Methods for covalently functionalizing semiconducting single walled carbon nanotubes and uses thereof

Abstract

The present disclosure provides single-walled carbon nanotubes (SWCNTs) covalently functionalized with a plurality of molecules derived from monomers (e.g., acrylate monomers, acrylamide monomers, and styrene monomers), alcohols, amines, amino acids, alkyls, heteroaromatics, aryls, or carboxylic acids, and methods for preparing the same via Fenton-like reactions. The functionalized SWCNTs of the present technology may be useful as near-infrared single-photon emitters, optical sensors, and as fluorophores for bioimaging and super-resolution microscopy.

Description

METHODS FOR COVALENTLY FUNCTIONALIZING SEMICONDUCTING SINGLE WALLED CARBON NANOTUBES AND USES THEREOF CROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U. S. Provisional Patent App. No. 63 / 718,439 filed on November 8, 2024, and U. S. Provisional Patent App. No. 63 / 794,993 filed on April 25, 2025, the disclosures of each of which are incorporated herein by reference in their entirety for all purposes.GOVERNMENT SUPPORT

[0002] This invention was made with government support under CA008748 awarded by the National Institutes of Health. The government has certain rights in the invention.TECHNICAL FIELD

[0003] The present disclosure provides single-walled carbon nanotubes (SWCNTs) covalently functionalized with a plurality of molecules derived from monomers (e.g., acrylate monomers, acrylamide monomers, and styrene monomers), alcohols, amines, amino acids, alkyls, heteroaromatics, aryls, or carboxylic acids, and methods for preparing the same via Fenton-like reactions. The functionalized SWCNTs of the present technology may be useful as near-infrared single-photon emitters, optical sensors, as fluorophores for bioimaging and super-resolution microscopy, and as single-photon emission applications.BACKGROUND

[0004] The following description of the background of the present technology is provided simply as an aid in understanding the present technology and is not admitted to describe or constitute prior art to the present technology.

[0005] Carbon nanotubes have several features which demonstrate their potential for biomedical applications including cellular sensing. For example, carbon nanotubes can be metallic or semiconducting depending on their structure, which is due to the symmetry and unique electronic structure of graphene. Thus, the electronic structure and diameter of thecarbon nanotube will determine the spectral characteristics seen in absorption, fluorescence, Raman scattering, etc. Moreover, the environmental sensitivity and intrinsic photostability of single-walled carbon nanotubes (SWCNTs) in the near-infrared wavelength range (ca. 900 nm-1600 nm) demonstrates the potential of biomedical applications. However, such uses require the ability to simultaneously modulate nanotube fluorescence and to biocompatibly derivatize the nanotube surface using noncovalent methods.

[0006] Non-covalent functionalization methods can be used to solubilize carbon nanotubes for adaption to biomedical applications. Non-covalent functionalization of SWCNTs preserves both the optical and structural properties of SWCNTs in solution. Nanotubes can be encapsulated in various amphiphilic polymers. Biopolymers such as single stranded DNA (ssDNA), peptides, or proteins, and synthetic polymers, such as polyfluorenes, polycarbazoles, aryleneethynylene polymers, polyethylene glycol (PEG) derivatives, and dextran-based polymers have been investigated for materials, and biological applications. However, encapsulation with biopolymers can produce higher background signal (e.g., DNA can produce high oxidation current and subsequently higher background currents) or provide inadequate control of coating the nanotube and therefore affect optical response (e.g., protein denaturation in unfavorable conditions). Moreover, the above-mentioned synthetic polymers do not provide controllable and / or tunable properties, which limit the ability to measure (e.g., via imaging) the kinetics of dynamic self-assembly and disassembly and translocation of photoluminescent nanotubes into live cell nuclei.

[0007] Therefore, there is a need to better adapt carbon nanotubes for biomedical applications, such as cellular imaging and sensing, that provides control over nanotube emission, environmental responsivity, precise control over sub-cellular localization, ordered surface coverage, and systematic modulation of nanotube optical properties.SUMMARY OF THE PRESENT TECHNOLOGY

[0008] In one aspect, the present disclosure provides a functionalized single-walled carbon nanotube (SWCNT) that (a) is covalently functionalized with a plurality of molecules and (b) exhibits luminescent sp3defects, wherein the functionalized SWCNT is para-functionalizedand / or ortho-functionalized, wherein the plurality of molecules that are covalently functionalized comprise one or more functional groups selected from among a boronic acid group, a carboxyl group, a hydroxyl group, an ester group, an amino group, an amide group, an aldehyde group, a ketone group, an ether group, an acrylate group, an acrylamide group, and a styrene group, and wherein the plurality of molecules that are covalently functionalized are derived from and / or comprise one or more of alcohols, amines, amides, aldehydes, ketones, amino acids, carboxylic acids, acrylate monomers, acrylamide monomers, substituted alkyls, unsubstituted alkyls, heteroaromatics, substituted aryls, unsubstituted aryls, sugars, styrene monomers, or target molecules. The plurality of molecules may comprise a nucleic acid, a peptide, or a protein. In certain embodiments, the functionalized SWCNT is a (6,5) SWCNT, a (7, 3) SWCNT, a (7, 5) SWCNT, or a (8, 4) SWCNT.

[0009] In some embodiments, the functionalized SWCNT is not encapsulated with a polymer or a surfactant. In other embodiments, the functionalized SWCNT is encapsulated with a polymer or a surfactant, and the plurality of molecules is not conjugated to the polymer or the surfactant. Examples of polymers include DNA (e.g., single stranded DNA (ssDNA)), LNAs, PNAs, peptides, proteins, polyfluorene, polycarbazole, aryleneethynylene polymers, polyethylene glycol (PEG) derivatives, or dextran-based polymers. Examples of surfactants include Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SUS), Sodium n-tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n-octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC). The polymer may be conjugated to the functionalized SWCNT directly or via a linker. In some embodiments, the linker comprises a 6 carbon (C6) linker, polyethylene glycol (PEG), a hydrocarbon, a synthetic polymer, or a biopolymer.

[0010] Additionally or alternatively, in some embodiments of the functionalized SWCNTs disclosed herein, the alcohols are primary alcohols, secondary alcohols, or tertiary alcohols. Examples of suitable alcohols include, but are not limited to, 1, 2, 4-butanetriol, 1, 2-propanediol, 1, 3-propanediol, 1, 4-butanediol, 1 -butanol, 1 -hexanol, 1 -pentanol, 1 -propanol, 2-m ethyl- 1 -propanol, 2-propanol, ethanol, methanol, phenol, and tert-butanol. Additionally or alternatively, in certain embodiments of the functionalized SWCNTs disclosed herein, the amines are primary amines, secondary amines, tertiary amines, aliphatic amines, or aromatic amines. Examples of suitable amines include 1, 2-diaminoethane, and tert-butyl amine.Additionally or alternatively, in some embodiments of the functionalized SWCNTs disclosed herein, the amino acids are naturally occurring amino acids, unnatural amino acids, L-amino acids, or D-amino acids. Examples of suitable amino acids include, but are not limited to, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the carboxylic acids are primary carboxylic acids, secondary carboxylic acids, tertiary carboxylic acids, aliphatic carboxylic acids, or aromatic carboxylic acids. Examples of suitable carboxylic acids include, but are not limited to, acetic acid, propionic acid, crotonic acid, and pivalic acid. In some embodiments, the acrylamide monomers are selected from among acrylamide, N, N-methylenebisacrylamide, 2-acrylamido-2-methylpropane sulfonic acid, 3-(acrylamido)phenylboronic acid, N-isopropyl acrylamide, and n-tert-butylacrylamide. In certain embodiments, the acrylate monomers are selected from among acrylic acid, methylacrylic acid, methacrylic acid, acryloxyethyl thiocarbamoyl rhodamine, 2, 2, 2, -trifluoroethyl methacrylate, and bis[2-(methacryloyloxy)ethyl] phosphate. In some embodiments, the target molecule may be selected from among sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, sodium deoxycholate, poly(N-isopropylacrylamide), maleimide, biotin, adenine, cytosine, guanine, thymine, uracil, dimethyl sulfoxide, lipoic acid, methanesulfonic acid, and ethanesulfonic acid.

[0011] In any and all embodiments of the functionalized SWCNTs disclosed herein, the functionalized SWCNT exhibits a detectable change in intrinsic fluorescence relative to a native SWCNT’s El l emission peak.

[0012] In one aspect, the present disclosure provides a SWCNT sensor comprising any and all embodiments of at least one functionalized SWCNT described herein.

[0013] In another aspect, the present disclosure provides a device comprising any and all embodiments of the at least one SWCNT sensor disclosed herein and a solid support on which the device is immobilized. The solid support may comprise a biocompatible gel, a microcapillary, a filter, a mesh, a tubing, a compartment / dialysis membrane, or a combination thereof. In some embodiments, the device comprises a microfluidic chamber containing the at least one SWCNT sensor, wherein the at least one SWCNT sensor is immobilized on a surface or contained in a semi-permeable enclosure. In some embodiments, the device is a sensor, or comprises a sensor, as described herein, and is a device for a non-medical application. In certain embodiments, the device is a device for monitoring environmental conditions.

[0014] In some embodiments, the SWCNT sensor may be used for single photon emission applications. When used for single-photon emission applications, the SWCNT sensor may radiate or emit one photon or single particles at a given time. The radiation of photons or particles from the SWCNT sensor may be controlled, such that a single photon or particle is transmitted over the given time. In some embodiments, the SWCNT sensor may be used for photon anti-bunching. The single photon emission applications may include, for example, single-photon emission imaging (e.g., single-photon emission computed tomography (SPECT), light detection and ranging (LiDAR), and quantum imaging) and quantum computing (e.g., quantum cryptography, quantum key distribution (QKD), quantum communication, and quantum information processing), among others.

[0015] In one aspect, the present disclosure provides a system comprising any and all embodiments of the device described herein, an excitation light source; and a detector for detecting light emitted from the at least one SWCNT sensor in the device following excitation by the excitation light source. In some embodiments of the system disclosed herein, the device comprises a biocompatible gel, a microcapillary, a filter, a mesh, a tubing, a compartment / dialysis membrane, and / or a solid support on or in which the at least one SWCNT sensor is immobilized. In certain embodiments, the excitation light source emits near-infrared light or light having a wavelength greater than 700 nm. Additionally or alternatively, in some embodiments of the system described herein, the detector detects fluorescent light. The devicemay be shaped and sized for subcutaneous, intraperitoneal, intrauterine, or intravenous implantation, or for delivery via injection. In any and all embodiments of the system described herein, the detector and the excitation light source are part of a unit. The unit may comprise a handheld unit positioned outside the subject or within a body cavity of the subject.

[0016] Additionally or alternatively, in some embodiments of the system described herein, the device is configured for attachment to or embedding within a wall of a body cavity, lumen, or organ. The body cavity, lumen, or organ may comprise a member selected from the group consisting of uterine cavity, cranial cavity, vertebral canal, thoracic cavity, abdominal cavity, pelvic cavity, artery, vein, gastrointestinal tract, bronchi, renal tubules, urinary collecting ducts, vagina, uterus, fallopian tubes, adrenal gland, bone, esophagus, heart, larynx, mouth, pituitary gland, muscle, spleen, thyroid, anus, brain, eye, hypothalamus, liver, nose, prostate, skin, stomach, ureter, appendix, gall bladder, kidney, lung, pancreas, rectum, small intestine, thymus, urethra, bladder, ear, genitals, large intestine, lymph node, parathyroid gland, salivary gland, spinal cord, and trachea.

[0017] In some embodiments, the at least one SWCNT sensor may emit the light in accordance with single-photon emission. In some embodiments, the device may include a quantum computer coupled with the detector to detect the light from the SWCNT sensor. In some embodiments, the device may use the light detected at the detector to perform at least one of quantum cryptography, quantum key distribution (QKD), quantum communication, or quantum information processing. In some embodiments, the device may include an imaging device coupled with the detector and configured to perform single-photon emission imaging. In some embodiments, the imaging device may use the light detected at the detector to perform the single-photon emission imaging in accordance with at least one of single-photon emission computed tomography (SPECT), light detection and ranging (LiDAR), or quantum imaging.

[0018] In another aspect, the present disclosure provides a kit comprising any and all embodiments of the functionalized SWCNT or the SWCNT sensor described herein, at least one container and instructions for use. The at least one container may be an ampule, a vial, a cartridge, a reservoir, a lyo-ject, or a pre- filled syringe.

[0019] In one aspect, the present disclosure provides a method for preparing functionalized SWCNTs comprising: incubating a plurality of native SWCNTs with a plurality of molecules in the presence of a Fenton-like metal and hydrogen peroxide under conditions that permit covalent attachment of the plurality of molecules to the native SWCNTs, wherein the plurality of molecules are selected from among alcohols, amines, amides, aldehydes, ketones, amino acids, carboxylic acids, substituted alkyls, unsubstituted alkyls, aromatics, heteroaromatics, substituted aryls, unsubstituted aryls, acrylate monomers, acrylamide monomers, sugars, styrene monomers, and target molecules. In some embodiments, the Fenton-like metal is Fe, Mn, Ce, Cu, Ag, or Mn. Additionally or alternatively, in some embodiments of the methods disclosed herein, the Fenton-like metal is derived from FeBn, Feb, ferrocene, ferrocene-derivatives (e.g. ferrocene carboxylic acid), iron(II) trifluoromethane sulfonic acid, FeCh, or Fe(III) tosylate.

[0020] Additionally or alternatively, in certain embodiments, the Fenton-like metal is present in a concentration that ranges from about 10 nM to about 35 pM. Additionally or alternatively, in some embodiments, the plurality of native SWCNTs are incubated with the plurality of molecules for about 5 minutes to about 12 hours.

[0021] In any of the preceding embodiments, the method further comprises encapsulating the plurality of native SWCNTs with a polymer or a surfactant, wherein the plurality of molecules are not conjugated to the polymer or the surfactant. Examples of polymers include DNA (e.g., single stranded DNA (ssDNA)), LNAs, PNAs, peptides, proteins, polyfluorene, polycarbazole, aryleneethynylene polymers, polyethylene glycol (PEG) derivatives, or dextran-based polymers. Examples of surfactants include Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SUS), Sodium n-tri decyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n-octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC). Alternatively, in some embodiments, the plurality of native SWCNTs or the functionalized SWCNTs are not encapsulated with a polymer or a surfactant.

[0022] Additionally or alternatively, in some embodiments of the methods disclosed herein, the alcohols are primary alcohols, secondary alcohols, or tertiary alcohols. Examples of suitablealcohols include, but are not limited to, 1, 2, 4-butanetriol, 1, 2-propanediol, 1, 3 -propanediol, 1, 4-butanediol, 1 -butanol, 1 -hexanol, 1 -pentanol, 1 -propanol, 2 -methyl- 1 -propanol, 2-propanol, ethanol, methanol, phenol, and tert-butanol. Additionally or alternatively, in certain embodiments of the methods disclosed herein, the amines are primary amines, secondary amines, tertiary amines, aliphatic amines, or aromatic amines. Examples of suitable amines include 1, 2-diaminoethane, and tert-butyl amine. Additionally or alternatively, in some embodiments of the methods disclosed herein, the amino acids are naturally occurring amino acids, unnatural amino acids, L-amino acids, or D-amino acids. Examples of suitable amino acids include, but are not limited to, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. In any of the preceding embodiments of the methods disclosed herein, the carboxylic acids are primary carboxylic acids, secondary carboxylic acids, tertiary carboxylic acids, aliphatic carboxylic acids, or aromatic carboxylic acids. Examples of suitable carboxylic acids include, but are not limited to, acetic acid, propionic acid, crotonic acid, and pivalic acid. In some embodiments, the acrylamide monomers are selected from among acrylamide, N, N-methylenebisacrylamide, 2-acrylamido-2-methylpropane sulfonic acid, 3-(acrylamido)phenylboronic acid, N-isopropylacrylamide, and n-tert-butyl acrylamide. In certain embodiments, the acrylate monomers are selected from among acrylic acid, methylacrylic acid, methacrylic acid, acryloxyethyl thiocarbamoyl rhodamine, 2, 2, 2, -trifluoroethyl methacrylate, and bis[2-(methacryloyloxy)ethyl] phosphate.

[0023] In any and all embodiments of the methods disclosed herein, the plurality of native SWCNTs are incubated with the plurality of molecules in the presence of UV or light irradiation.

[0024] The SWCNT sensors or devices of the present technology may be used in a variety of applications such as near-infrared single-photon emitters at room temperature, in electroluminescent devices as versatile optical sensors, and as fluorophores for bioimaging and potential super-resolution microscopy. In certain embodiments, the device is a sensing platform.

[0025] In one aspect, the present disclosure provides an imaging method comprising contacting any and all embodiments of the SWCNT sensor disclosed herein with a chemical or abiological sample to form a mixture; exposing the mixture to excitation light; and detecting light emitted by the at least one SWCNT sensor in the mixture following excitation by the excitation light. In another aspect, the present disclosure provides an imaging method comprising administering any and all embodiments of the SWCNT sensor disclosed herein to a subject; exposing the subject to excitation light; and detecting light emitted by the at least one SWCNT sensor in the subject following excitation by the excitation light. In certain embodiments of the methods, the detecting comprises obtaining images of cells or tissue of the biological sample or the subject.

[0026] In one aspect, the present disclosure provides a method of performing single-photon emissions. The method may include providing the SWCNT sensor disclosed herein; exposing the SWCNT sensor to excitation light; and detecting light emitted by the at least one SWCNT sensor in accordance with single-photon emissions. In some embodiments, the method may include performing a quantum computing function using the light emitted by the at least one SWCNT sensor. In some embodiments, the quantum computing function comprises at least one of quantum cryptography, quantum key distribution (QKD), quantum communication, or quantum information processing. In some embodiments, the method may include performing single-photon emission imaging using the light emitted by the at least one SWCNT sensor. In some embodiments, the single-photon emission imaging may include at least one of singlephoton emission computed tomography (SPECT), light detection and ranging (LiDAR), or quantum imaging.

[0027] In one aspect, the present disclosure provides a method for preparing functionalized SWCNTs comprising: incubating a plurality of native SWCNTs with a plurality of molecules in the presence of heat and hydrogen peroxide under conditions that permit covalent attachment of the plurality of molecules to the native SWCNTs, wherein the plurality of molecules are selected from among alcohols, amines, amides, aldehydes, ketones, amino acids, carboxylic acids, alkyls, aromatics, heteroaromatics, aryls, acrylate monomers, acrylamide monomers, sugars, styrene monomers, and target molecules. Additionally or alternatively, in some embodiments, the plurality of native SWCNTs are incubated with the plurality of molecules for about 5 minutes toabout 35 minutes. In some embodiments, the plurality of native SWCNTs are heated to a temperature ranging from 22°C-60°C. In any of the preceding embodiments, the method further comprises encapsulating the plurality of native SWCNTs with a polymer or a surfactant, wherein the plurality of molecules are not conjugated to the polymer or the surfactant. Examples of polymers include DNA (e.g., single stranded DNA (ssDNA)), LNAs, PNAs, peptides, proteins, polyfluorene, polycarbazole, aryleneethynylene polymers, polyethylene glycol (PEG) derivatives, or dextran-based polymers. Examples of surfactants include Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SUS), Sodium n-tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n-octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC). Alternatively, in some embodiments, the plurality of native SWCNTs or the functionalized SWCNTs are not encapsulated with a polymer or a surfactant.

[0028] Aspects of the present disclosure are directed to methods of classifying molecules of interest. The method may include contacting a sample having molecules of interest with a plurality of SWCNT sensors as disclosed herein, with each of the plurality of SWCNT sensors having a respective fluorescence response profile in reacting to the sample. The method may include emitting fluorescent light toward the plurality of SWCNT sensors to illuminate a sample having molecules of interest. The method may include acquiring, by an imaging device, an image of a plurality of light signals corresponding to the plurality of SWCNT sensors. The method may include receiving, by a computing system, via the imaging device, the image of the plurality of light signals from the plurality of SWCNT sensors. The method may include generating, by the computing system, using the plurality of light signals of the image, a response code defining a plurality of responses by the corresponding plurality of SWCNT sensors to the fluorescent light due to the respective fluorescence response profile in each SWCNT sensor of the plurality of SWCNT sensors. The method may include determining, by the computing system, a classification of the molecules of interest of the sample based on the response code. The method may include providing, by the computing system, an output to identify the classification of the molecules of interest of the sample.

[0029] In some embodiments, the classification may identify at least one of: presence or extent of disease, presence or type of pathogenic organisms, presence of risk factors or comorbidities, prediction of prognosis, or clinically relevant parameters. In some embodiments, the classification may identify at least one of: presence or concentration of toxic compounds, drugs, or environmental pollutants. In some embodiments, the classification may identify at least one of: pH level, salt level or salt type, redox species, concentration of oxygen or other gas, temperature, presence of contaminants, or type of cells present. In some embodiments, the sample may include at least one of a cell or a cell growth medium, and the classification may identify at least one of: a presence or concentration of nutrients, presence or concentration of metabolites, cell confluency; pH, presence, or concentration of toxins, or a biological parameter.

[0030] Aspects of the present disclosure are directed to methods of validating authenticity of samples. The method may include emitting, by a light source, fluorescent light to illuminate a sample in contact with a plurality of SWCNT sensors as disclosed herein arranged in accordance with a pattern, with each of the plurality of SWCNT sensors having a respective fluorescence response profile in reacting to the sample. The method may include acquiring, by an imaging device, an image of a plurality of light signals corresponding to the plurality of SWCNT sensors, the plurality of light signals capturing the pattern on the sample. The method may include receiving, by a computing system, via the imaging device, the image of the plurality of light signals from the plurality of SWCNT sensors. The method may include generating, by the computing system, using the plurality of light signals of the image, a response code corresponding to the pattern, the response code defining a plurality of responses by the corresponding plurality of SWCNT sensors to the fluorescent light due to the respective fluorescence response profile in each SWCNT sensor of the plurality of SWCNT sensors. The method may include determining, by the computing system, a validation of the sample as one of authenticated or unauthenticated based on the response code. The method may include providing, by the computing system, an output to identify the validation of the sample as one of authenticated or unauthenticated. In some embodiments, the pattern may be configured to at least one of: (i) establish an identity, (ii) validate an authenticity, or (iii) track a chain of ownership of the sample.BRIEF DESCRIPTION OF THE DRAWINGS

[0031] FIG. 1 shows emission spectra of exemplary covalent conjugation of small molecules (e.g., alcohols, amines, amino acids, carboxylic acids, monomers (e.g., acrylate monomers, acrylamide monomers, and styrene monomers), alkyls, aryls, heteroaromatics) to unwrapped SWCNTs via Fenton reactions. The functionalized nanotubes are subsequently wrapped with sodium deoxycholate (DOC) to facilitate fluorescence. The aryl and alkyl defects were prepared using boronic acids (at the 1 -position), whereas the heteroaromatics were conjugated directly.

[0032] FIG. 2 shows spectra showing the functionalization of SWCNTs with valine via Fenton reactions at different temperatures, to show the temperature dependence of 1150 nm / 1250 nm peak formation. FIG.2 includes un-normalized and normalized spectra at different temperatures relative to the 1150 and 1250 peak emission. The SWCNTs were unwrapped at time of functionalization, and then wrapped with DOC to facilitate fluorescence measurement.

[0033] FIG. 3 shows spectra showing the functionalization of SWCNTs with 1-propanol via Fenton reactions at different temperatures, to show the temperature dependence of 1150 nm / 1250 nm peak formation. The SWCNTs were unwrapped at time of functionalization, and then wrapped with DOC to facilitate fluorescence measurement. FIG.3 includes un-normalized and normalized spectra at different temperatures relative to the 1150 and 1250 peak emission. The trend of increased intensity at 1150 nm relative to 1250 nm at higher temperatures is evident on the 1250-normalized graph.

[0034] FIG. 4 shows exemplary structures of SWCNTs covalently functionalized with propanol via Fenton reactions.

[0035] FIG. 5 shows exemplary structures of SWCNTs covalently functionalized with ethylamine via Fenton reactions.

[0036] FIG. 6 shows exemplary structures of SWCNTs covalently functionalized with propionic acid via Fenton reactions.

[0037] FIG. 7 shows exemplary structures of SWCNTs covalently functionalized with threonine via Fenton reactions.

[0038] FIGs. 8A depicts a block diagram of an example system including a SWCNT sensor, in accordance with one or more implementations.

[0039] FIG. 8B depicts a block diagram of an example system to process light from a SWCNT sensor, in accordance with one or more implementations.

[0040] FIG. 9 shows plot showing fluorescence spectrum of DNA- wrapped SWCNTs treated with H2O2 in the presence of no additive, FeCl₂, or FeCl₂ and ethanol.

[0041] FIG. 10 shows exemplary structures of SWCNTs covalently functionalized with aryls and alkyls via Fenton reactions. FIG. 10 shows potential spectra of ortho-configuration alcohols (first two rows), ortho alkyl defects (third row), ortho aryl defects (fourth) and para aryl defects (fifth).

[0042] FIGs. 11A-11C show that peroxide-mediated functionalization can proceed in the absence of iron or other Fenton metals at higher temperature, dependent on the choice of molecule functionalized. Notably, the ratio of ortho (1150) to para (1250) appears different in the presence vs absence of iron (as shown by 1 -propanol compared to the iron-present samples described herein). FIGs. 11A-11C show the functionalization of SWCNTs with 1-propanol, acrylic acid and 4-nitrophenyl boronic acid (representing one example of hydrogen abstraction-mediated functionalization, one of radical addition to the monomer, one of deboronation) at various temperatures in the absence of iron (presumably peroxide is decomposing to hydroxyl radicals due to heat).

[0043] FIG. 12 depicts a block diagram of a server system and a client computer system, in accordance with one or more implementations.

[0044] FIG. 13 shows emission spectra of CCNTs functionalized with various alcohols, aldehydes, carboxylic acids and amides, normalized to E11 emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0045] FIG. 14 depicts emission spectra of CCNTs functionalized with various alcohols, aldehydes, carboxylic acids and amides, normalized to E11 emission intensity. Control spectracorresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0046] FIG. 15 depicts emission spectra of CCNTs functionalized with various fluorinated aliphatic molecules, normalized to En emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0047] FIG. 16 depicts emission spectra of CCNTs functionalized with various aliphatic molecules, normalized to En emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0048] FIG. 17 depicts emission spectra of CCNTs functionalized with various amino acids, normalized to En emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0049] FIG. 18 depicts emission spectra of CCNTs functionalized with various acrylates acrylamide derivatives, and carboxylic acids, normalized to En emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0050] FIG. 19 depicts emission spectra of CCNTs functionalized with various aromatic molecules, normalized to En emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0051] FIG. 20 depicts emission spectra of CCNTs functionalized with various alkyl or aryl boronic acids, normalized to En emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0052] FIG. 21 depicts emission spectra of CCNTs functionalized with various alkyl or aryl boronic acids, normalized to En emission intensity. Control spectra corresponding to SWCNTstreated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0053] FIG. 22 depicts emission spectra of CCNTs functionalized with various other molecules of chemical or biological interest, normalized to En emission intensity. Control spectra corresponding to SWCNTs treated with functionalization reaction without an added conjugation substrate are shown as dotted lines.

[0054] FIG. 23 depicts spectra showing the functionalization of SWCNTs with propionic acid at different iron chloride concentrations to show an effect of iron on SWCNT functionalization. The SWNCTs were wrapped with DOC to facilitate fluorescence measurement. FIG. 23 includes un-normalized (top) and normalized (bottom) spectra at different iron chloride concentrations.

[0055] FIG. 24 depicts spectra showing the functionalization of SWCNTs with tert-Butyl alcohol at different iron chloride concentrations to show an effect of iron on SWCNT functionalization. The SWNCTs were wrapped with DOC to facilitate fluorescence measurement. FIG.24 includes un-normalized (top) and normalized (bottom) spectra at different iron chloride concentrations.

[0056] FIG. 25 depicts a Raman spectra of tert-Butyl alcohol functionalized nanotubes prepared at different concentrations of iron chloride. FIG.25 depicts a graph showing functionalization results growth of the disorder (D) band at ~1310 cm-1associated with sp3-hybridized carbon sites on the nanotube sidewall, relative to the graphene (G) band at ~1590 cm-1The growth of the D band therefore correlates with the degree of functionalization, as represented by the ratio of D: G band integrals.

[0057] FIG. 26 depicts a spectra of the environmental sensitivity of functionalized nanotubes. Solutions including functionalized SWCNTs were mixed with each of: presepsin (1,000 ng / mL), C-reactive protein (CRP, 1 mg / mL), azurocidin (1,000 ng / mL), water (control), procalcitonin (PCT, 20 ng / mL), leptin (40 ng / mL), interleukin-6 (IL6, 800 pg / mL) or lactic acid (10 mM). The fluorescence spectra was measured for each solution.

[0058] FIG. 27 depicts exemplary structures of aryl-functionalized nanotubes in ortho or para configurations. Examples of R’-R10groups could include COOH, OMe, NO2, SO3H, Me, Et, NH2, NMe2, NEt2 among others.DETAILED DESCRIPTION

[0059] It is to be appreciated that certain aspects, modes, embodiments, variations and features of the present methods are described below in various levels of detail in order to provide a substantial understanding of the present technology.

[0060] In practicing the present methods, many conventional techniques in molecular biology, protein biochemistry, cell biology, immunology, microbiology and recombinant DNA are used. See, e.g., Sambrook and Russell eds. (2001) Molecular Cloning: A Laboratory Manual, 3rd edition; the series Ausubel et al. eds. (2007) Current Protocols in Molecular Biology, the series Methods in Enzymology (Academic Press, Inc., N. Y.); MacPherson et al. (1991) PCR 1: A Practical Approach (IRL Press at Oxford University Press); MacPherson el al (1995) PCR 2: A Practical Approach,' Harlow and Lane eds. (1999) Antibodies, A Laboratory Manual,' Freshney (2005) Culture of Animal Cells: A Manual of Basic Technique, 5th edition; Gait ed. (1984) Oligonucleotide Synthesis,' U. S. Patent No. 4,683,195; Hames and Higgins eds. (1984) Nucleic Acid Hybridization,' Anderson (1999) Nucleic Acid Hybridization, Hames and Higgins eds. (1984) Transcription and Translation; Immobilized Cells and Enzymes (IRL Press (1986)); Perbal (1984) A Practical Guide to Molecular Cloning; Miller and Calos eds. (1987) Gene Transfer Vectors for Mammalian Cells (Cold Spring Harbor Laboratory); Makrides ed. (2003) Gene Transfer and Expression in Mammalian Cells; Mayer and Walker eds. (1987) Immunochemical Methods in Cell and Molecular Biology (Academic Press, London); and Herzenberg et al. eds (1996) Weir ’s Handbook of Experimental Immunology. Methods to detect and measure levels of polypeptide gene expression products (i.e., gene translation level) are well-known in the art and include the use of polypeptide detection methods such as antibody detection and quantification techniques. (See also, Strachan & Read, Human Molecular Genetics, Second Edition. (John Wiley and Sons, Inc., NY, 1999)).

[0061] Disclosed herein are single- walled carbon nanotubes (SWCNTs) covalently functionalized with a plurality of molecules derived from monomers (e.g., acrylate monomers, acrylamide monomers, and styrene monomers), alcohols, amines, amino acids, alkyls, heteroaromatics, aryls, or carboxylic acids, and methods for preparing the same via Fenton-like reactions. The functionalized SWCNTs of the present technology may be useful as near-infrared single-photon emitters, optical sensors, as fluorophores for bioimaging and super-resolution microscopy, and as single-photon emission applications.

[0062] The relative conformation of sp3centers on a SWCNT dictates its fluorescence properties - if the two "defects" (sp3centers) are on adjacent carbon atoms ("ortho" conformation), then the nanotubes exhibit a second fluorescence peak -160 nm red-shifted relative to the nanotube's native emission peak (at 1150 nm in the case of the most common chirality of nanotube, (6,5)). If the two sp3centers are spaced 3 carbon atoms apart ("para" conformation), then a fluorescence emission peak forms -260 nm red-shifted relative to the native peak (at 1250 nm in the case of (6,5) nanotubes). Accordingly, the reaction methods disclosed herein are able to conjugate inert small molecules (typically alcohols and amines) onto nanotubes to generate either type of defect peak, dependent on the nature of the small molecule. The ratio of the two emission peaks can be controlled through either choice of small molecule for conjugation, or control of the environment (e.g. temperature).

[0063] These results were surprising because while the Fenton reaction using Fe(II) salts in the presence of H2O2 was used in the past to covalently functionalize carbon nanotubes, the harsh reaction conditions and thus extensive functionalization prevented the observation of potential luminescent defects. Settele el al., ACS Nano (2024) 18, 20667-20678 (“However, when trying to perform the original Fenton reaction with Fe(II / III) salts and (6,5) SWNTs, we find that Fe(III) ions are unsuitable for functionalization, most likely due to the efficient p-doping of SWNTs and thus PL quenching”). Without wishing to be bound by theory, it is believed that conditions such as Fenton-like metal concentrations, incubation times, or pre-wrapping of SWCNTs with a surfactant or polymer, may adversely impact functionalization of the SWCNTs (either by directly conjugating the surfactant, by shielding the nanotube too effectively from theiron, or by otherwise coordinating to the Fenton-like metal). The methods of the present technology perform Fenton-reactions on unwrapped or DNA wrapped nanotubes thus rendering the SWCNT surface more accessible to the Fenton-metals.Definitions

[0064] Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. As used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise. For example, reference to “a cell” includes a combination of two or more cells, and the like.Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry, analytical chemistry and nucleic acid chemistry and hybridization described below are those well-known and commonly employed in the art.

[0065] In this application, the use of “or” means “and / or” unless stated otherwise. As used in this application, the term “comprise” and variations of the term, such as “comprising” and “comprises,” are not intended to exclude other additives, components, integers or steps.

[0066] As used herein, the term “about” in reference to a number is generally taken to include numbers that fall within a range of 1%, 5%, 10%, or 15% in either direction (greater than or less than) of the number unless otherwise stated or otherwise evident from the context (except where such number would be less than 0% or exceed 100% of a possible value).

[0067] As used herein, the “administration” of an agent or drug to a subject includes any route of introducing or delivering to a subject a compound to perform its intended function. Administration can be carried out by any suitable route, including but not limited to, orally, intranasally, parenterally (intravenously, intramuscularly, intraperitoneally, or subcutaneously), rectally, intrathecally, or topically. Administration includes self-admini strati on and the administration by another.

[0068] As used herein, “aliphatic” groups include straight and branched chain alkyl groups, alkenyl groups, and alkynyl groups. Aliphatic groups may be saturated aliphatic groups or unsaturated aliphatic groups. Saturated aliphatic groups include straight and branched chain alkyl groups. Unsaturated aliphatic groups include straight and branched chain alkenyl groups and alkynyl groups. Aliphatic groups may be substituted or unsubstituted. Aliphatic groups may have 1 to 12 carbon atoms, and typically from 2 to 10 carbon atoms, or in some embodiments, from 2 to 8, 2 to 6, or 2 to 4 carbon atoms. Representative substituted aliphatic groups may be mono substituted or substituted more than once, such as, but not limited to, mono-, di- or trisubstituted with substituents such as those listed above.

[0069] As used herein, the term “analyte” broadly refers to any substance to be analyzed, detected, measured, or quantified. Examples of analytes include, but are not limited to, proteins, peptides, hormones, haptens, antigens, antibodies, receptors, enzymes, nucleic acids, polysaccharides, chemicals, polymers, pathogens, toxins, organic drugs, inorganic drugs, cells, tissues, microorganisms, viruses, bacteria, fungi, algae, parasites, allergens, pollutants, and combinations thereof.

[0070] As used herein, the term “associated” typically refers to two or more entities in physical proximity with one another, either directly or indirectly (e.g., via one or more additional entities that serve as a linking agent), to form a structure that is sufficiently stable so that the entities remain in physical proximity under relevant conditions, e.g., physiological conditions. In some embodiments, associated moieties are covalently linked to one another. In some embodiments, associated entities are non-covalently linked. In some embodiments, associated entities are linked to one another by specific non-covalent interactions (e.g., by interactions between interacting ligands that discriminate between their interaction partner and other entities present in the context of use, such as, for example, streptavidin / avidin interactions, antibody / antigen interactions, etc.). Alternatively or additionally, a sufficient number of weaker non-covalent interactions can provide sufficient stability for moieties to remain associated. Exemplary “non-covalent” interactions include, but are not limited to, electrostatic interactions, hydrogen bonding, affinity, metal coordination, physical adsorption, host-guest interactions,hydrophobic interactions, pi stacking interactions, van der Waals interactions, magnetic interactions, electrostatic interactions, dipole-dipole interactions, etc.

[0071] As used herein, the term “cancer” refers to a disease, disorder, or condition in which cells exhibit relatively abnormal, uncontrolled, and / or autonomous growth, so that they display an abnormally elevated proliferation rate and / or aberrant growth phenotype characterized by a significant loss of control of cell proliferation. In certain embodiments, a cancer may be characterized by one or more tumors. Those skilled in the art are aware of a variety of types of cancer including, for example, adrenocortical carcinoma, astrocytoma, basal cell carcinoma, carcinoid, cardiac, cholangiocarcinoma, chordoma, chronic myeloproliferative neoplasms, craniopharyngioma, ductal carcinoma in situ, ependymoma, intraocular melanoma, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), gestational trophoblastic disease, glioma, histiocytosis, leukemia (e.g., acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), hairy cell leukemia, myelogenous leukemia, myeloid leukemia), lymphoma (e.g., Burkitt lymphoma [non-Hodgkin lymphoma], cutaneous T-cell lymphoma, Hodgkin lymphoma, mycosis fungoides, Sezary syndrome, AIDS-related lymphoma, follicular lymphoma, diffuse large B-cell lymphoma), melanoma, merkel cell carcinoma, mesothelioma, myeloma (e.g., multiple myeloma), myelodysplastic syndrome, papillomatosis, paraganglioma, pheochromacytoma, pleuropulmonary blastoma, retinoblastoma, sarcoma (e.g., Ewing sarcoma, Kaposi sarcoma, osteosarcoma, rhabdomyosarcoma, uterine sarcoma, vascular sarcoma), Wilms' tumor, and / or cancer of the adrenal cortex, anus, appendix, bile duct, bladder, bone, brain, breast, bronchus, central nervous system, cervix, colon, endometrium, esophagus, eye, fallopian tube, gall bladder, gastrointestinal tract, germ cell, head and neck, heart, intestine, kidney (e.g., Wilms' tumor), larynx, liver, lung e.g., non-small cell lung cancer, small cell lung cancer), mouth, nasal cavity, oral cavity, ovary, pancreas, rectum, skin, stomach, testes, throat, thyroid, penis, pharynx, peritoneum, pituitary, prostate, rectum, salivary gland, ureter, urethra, uterus, vagina, or vulva.

[0072] As used herein, the term “covalent functionalization” refers to a process that involves attaching a functional group to a material through a covalent bond. Specifically,functionalization of a material with a substance would entail formation of chemical bonds between the material and substance by the sharing of electrons between atoms of the material and the substance.

[0073] As used herein, the term “detector” includes any detector of electromagnetic radiation including, but not limited to, CCD cameras, photodiodes, optical sensors, and infrared detectors. In some embodiments, detection of one or more analytes is achieved by measuring changes in fluorescence intensity, shifts in fluorescence wavelength, and / or other characteristics in the spectral characteristics of the described compositions.

[0074] As used herein, the term “functionalization” refers to any process of modifying a material by bringing physical, chemical or biological characteristics different from the ones originally found on the material. Typically, functionalization involves introducing functional groups to the material. As used herein, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. As used herein, functional groups include both chemical (e.g., ester, carboxylate, alkyl) and biological groups (e.g, adapter, or linker sequences). In some embodiments, click reactive groups are used (for ‘click chemistry’). Examples of click reactive groups include the following: alkyne, azide, thiol (sulfydryl), alkene, acrylate, oxime, maliemide, NHS (N-hydroxysuccinimide), amine (primary amine, secondary amine, tertiary amine, and / or quarternary ammonium), phenyl, benzyl, hydroxyl, carbonyl, aldehyde, carbonate, carboxylate, carboxyl, ester, methoxy, hydroperoxy, peroxy, ether, hemiacetal, hemiketal, acetal, ketal, orthoester, orthocarbonate ester, amide, carboxyamide, imine (primary ketimine, secondary ketamine, primary aldimine, secondary aldimine), imide, azo (diimide), cyanate (cyanate or isocyanate), nitrate, nitrile, isonitrile, nitrite (nitrosooxy group), nitro, nitroso, pyridyl, sulfide, disulfide, sulfinyl, sulfonyl, sulfino, sulfo, thiocyanate, isothiocyanate, caronothioyl, thione, thial, phosphine, phosphono, phosphate, phosphodiester, borono, boronate, bornino, borinate, halo, fluoro, chloro, bromo, and / or iodo moieties.

[0075] As used herein, the terms “individual”, “patient”, or “subject” can be an individual organism, a vertebrate, a mammal, or a human. In some embodiments, the individual, patient or subject is a human.

[0076] As used herein, the term “luminescent sp3defects,” also known as organic color centers (OCCs), are atomic defects that can be synthetically created in single-walled carbon nanotube hosts to enable the emission of shortwave infrared single photons at room temperature. These defects are generally created by covalently attaching low-density chemical functional groups, such as aryl and alkyl groups, to the native SWCNTs.

[0077] As used herein, the term “non-encapsulated nanotube” refers to a nanotube which is not enclosed by or wrapped with a biopolymer, a detergent or surfactant.

[0078] As used herein, the term “polynucleotide” or “nucleic acid” means any RNA or DNA, which may be unmodified or modified RNA or DNA. Polynucleotides include, without limitation, single- and double-stranded DNA, DNA that is a mixture of single- and doublestranded regions, single- and double-stranded RNA, RNA that is mixture of single- and doublestranded regions, and hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, polynucleotide refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. In some embodiments, a nucleic acid is, comprises, or consists of one or more natural nucleic acid residues. In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleic acid analogs. In some embodiments, a nucleic acid analog differs from a nucleic acid in that it does not utilize a phosphodiester backbone. For example, in some embodiments, a nucleic acid is, comprises, or consists of one or more “peptide nucleic acids”, which are known in the art and have peptide bonds instead of phosphodiester bonds in the backbone, are considered within the scope of the present technology. Alternatively or additionally, in some embodiments, a nucleic acid has one or more phosphorothioate and / or 5'-N-phosphoramidite linkages rather than phosphodiester bonds. In some embodiments, a nucleic acid is, comprises, or consists of one ormore natural nucleosides (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxy guanosine, and deoxycytidine). In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C 5 -iodouridine, C5-propynyl-uridine, C5 -propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, 6-O-methylguanine, 2-thiocytidine, methylated bases, intercalated bases, and combinations thereof). In some embodiments, a nucleic acid comprises one or more modified sugars (e.g., 2 '-fluororibose, ribose, 2'-deoxyribose, arabinose, and hexose) as compared with those in natural nucleic acids. In some embodiments, a nucleic acid has a nucleotide sequence that encodes a functional gene product such as an RNA or protein. In some embodiments, a nucleic acid includes one or more introns. In some embodiments, nucleic acids are prepared by one or more of isolation from a natural source, enzymatic synthesis by polymerization based on a complementary template (in vivo or in vitro), reproduction in a recombinant cell or system, and chemical synthesis. In some embodiments, a nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 1 10, 120, 130, 140, 150, 160, 170, 180, 190, 20, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 or more residues long. In some embodiments a nucleic acid has a nucleotide sequence comprising at least one element that encodes, or is the complement of a sequence that encodes, a polypeptide. In some embodiments, a nucleic acid has enzymatic activity.

[0079] As used herein, the terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to mean a polymer comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres. Polypeptide refers to both short chains, commonly referred to as peptides, glycopeptides or oligomers, and to longer chains, generally referred to as proteins. Polypeptides may contain amino acids other than the 20 gene-encoded amino acids. Polypeptides include amino acid sequences modified either by natural processes, such as post-translational processing, or by chemical modification techniquesthat are well known in the art. In certain embodiments, one or more of the amino acids in a protein may be modified, for example, by the addition of a chemical entity such as a carbohydrate group, a phosphate group, a farnesyl group, an isofamesyl group, a fatty acid group, a linker for conjugation, functionalization, or other modification, etc. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Polypeptides may contain L-amino acids, D-amino acids, or both and may contain any of a variety of amino acid modifications or analogs known in the art. Useful modifications include, e.g., terminal acetylation, amidation, methylation, etc. In some embodiments, proteins may comprise natural amino acids, non-natural amino acids, synthetic amino acids, and combinations thereof. The term “peptide” is generally used to refer to a polypeptide having a length of less than about 100 amino acids, less than about 50 amino acids, less than 20 amino acids, or less than 10 amino acids.

[0080] As used herein, the term “sample” refers to clinical samples obtained from a subject. Biological samples may include tissues, cells, protein or membrane extracts of cells, mucus, sputum, bone marrow, bronchial alveolar lavage (BAL), bronchial wash (BW), and biological fluids (e.g., ascites fluid or cerebrospinal fluid (CSF)) isolated from a subject, as well as tissues, cells and fluids (blood, plasma, saliva, urine, serum etc present within a subject.

[0081] In general, “substituted” refers to an organic group as defined below (e.g., an alkyl group) in which one or more bonds to a hydrogen atom contained therein are replaced by a bond to non-hydrogen or non-carbon atoms. Substituted groups also include groups in which one or more bonds to a carbon(s) or hydrogen(s) atom are replaced by one or more bonds, including double or triple bonds, to a heteroatom. Thus, a substituted group is substituted with one or more substituents, unless otherwise specified. In some embodiments, a substituted group is substituted with 1, 2, 3, 4, 5, or 6 substituents. Examples of substituent groups include: halogens (i.e., F, Cl, Br, and I); hydroxyls; alkoxy, alkenoxy, aryloxy, aralkyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, and heterocyclylalkoxy groups; carbonyls (oxo); carboxylates; esters; urethanes; oximes; hydroxylamines; alkoxyamines; aralkoxyamines; thiols; sulfides; sulfoxides; sulfones; sulfonyls; pentafluorosulfanyl (i.e., SFs), sulfonamides; amines; N-oxides; hydrazines;hydrazides; hydrazones; azides; amides; ureas; amidines; guanidines; enamines; imides; isocyanates; isothiocyanates; cyanates; thiocyanates; imines; nitro groups; nitriles (z.e., CN); and the like.

[0082] Substituted ring groups such as substituted cycloalkyl, aryl, heterocyclyl and heteroaryl groups also include rings and ring systems in which a bond to a hydrogen atom is replaced with a bond to a carbon atom. Therefore, substituted cycloalkyl, aryl, heterocyclyl and heteroaryl groups may also be substituted with substituted or unsubstituted alkyl, alkenyl, and alkynyl groups as defined below.

[0083] As used herein, Cx-Cy, such as C1-C12, Ci-Cs, or Ci-Ce when used before a group refers to that group containing x toy’ carbon atoms.

[0084] Alkyl groups include straight chain and branched chain alkyl groups having from 1 to 12 carbon atoms, and typically from 1 to 10 carbons or, in some embodiments, from 1 to 8, 1 to 6, or 1 to 4 carbon atoms. Alkyl groups may be substituted or unsubstituted. Examples of straight chain alkyl groups include groups such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, and n-octyl groups. Examples of branched alkyl groups include, but are not limited to, isopropyl, iso-butyl, sec-butyl, tert-butyl, neopentyl, isopentyl, and 2,2-dimethylpropyl groups. Representative substituted alkyl groups may be substituted one or more times with substituents such as those listed above, and include without limitation haloalkyl (e.g., trifluoromethyl), hydroxyalkyl, thioalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxyalkyl, carboxyalkyl, and the like.

[0085] Cycloalkyl groups include mono-, bi- or tricyclic alkyl groups having from 3 to 12 carbon atoms in the ring(s), or, in some embodiments, 3 to 10, 3 to 8, or 3 to 4, 5, or 6 carbon atoms. Cycloalkyl groups may be substituted or unsubstituted. Exemplary monocyclic cycloalkyl groups include, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups. In some embodiments, the cycloalkyl group has 3 to 8 ring members, whereas in other embodiments the number of ring carbon atoms range from 3 to 5, 3 to 6, or 3 to 7. Bi- and tricyclic ring systems include both bridged cycloalkyl groups and fused rings, such as, but not limited to, bicyclo[2.1.1]hexane, adamantyl, decalinyl, and the like.Substituted cycloalkyl groups may be substituted one or more times with non-hydrogen and noncarbon groups as defined above. However, substituted cycloalkyl groups also include rings that are substituted with straight or branched chain alkyl groups as defined above. Representative substituted cycloalkyl groups may be mono-substituted or substituted more than once, such as, but not limited to, 2,2-, 2,3-, 2,4- 2,5- or 2,6-disubstituted cyclohexyl groups, which may be substituted with substituents such as those listed above.

[0086] Cycloalkylalkyl groups are alkyl groups as defined above in which a hydrogen or carbon bond of an alkyl group is replaced with a bond to a cycloalkyl group as defined above. Cycloalkylalkyl groups may be substituted or unsubstituted. In some embodiments, cycloalkylalkyl groups have from 4 to 16 carbon atoms, 4 to 12 carbon atoms, and typically 4 to 10 carbon atoms. Substituted cycloalkylalkyl groups may be substituted at the alkyl, the cycloalkyl or both the alkyl and cycloalkyl portions of the group. Representative substituted cycloalkylalkyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di- or tri-substituted with substituents such as those listed above.

[0087] Alkenyl groups include straight and branched chain alkyl groups as defined above, except that at least one double bond exists between two carbon atoms. Alkenyl groups may be substituted or unsubstituted. Alkenyl groups have from 2 to 12 carbon atoms, and typically from 2 to 10 carbons or, in some embodiments, from 2 to 8, 2 to 6, or 2 to 4 carbon atoms. In some embodiments, the alkenyl group has one, two, or three carbon-carbon double bonds. Examples include, but are not limited to vinyl,allyl, -CH=CH(CH3), -CH=C(CH3)2, -C(CH3)=CH2, -C(CH3)=CH(CH3), -C(CH2CH3)=CH2, among others. Representative substituted alkenyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di- or tri-substituted with substituents such as those listed above.

[0088] Cycloalkenyl groups include cycloalkyl groups as defined above, having at least one double bond between two carbon atoms. Cycloalkenyl groups may be substituted or unsubstituted. In some embodiments the cycloalkenyl group may have one, two or three double bonds but does not include aromatic compounds. Cycloalkenyl groups have from 4 to 14 carbonatoms, or, in some embodiments, 5 to 14 carbon atoms, 5 to 10 carbon atoms, or even 5, 6, 7, or 8 carbon atoms. Examples of cycloalkenyl groups include cyclohexenyl, cyclopentenyl, cyclohexadienyl, cyclobutadienyl, and cyclopentadienyl.

[0089] Cycloalkenylalkyl groups are alkyl groups as defined above in which a hydrogen or carbon bond of the alkyl group is replaced with a bond to a cycloalkenyl group as defined above. Cycloalkenyl alkyl groups may be substituted or un substituted. Substituted cycloalkenyl alkyl groups may be substituted at the alkyl, the cycloalkenyl or both the alkyl and cycloalkenyl portions of the group. Representative substituted cycloalkenylalkyl groups may be substituted one or more times with substituents such as those listed above.

[0090] Alkynyl groups include straight and branched chain alkyl groups as defined above, except that at least one triple bond exists between two carbon atoms. Alkynyl groups may be substituted or unsubstituted. Alkynyl groups have from 2 to 12 carbon atoms, and typically from 2 to 10 carbons or, in some embodiments, from 2 to 8, 2 to 6, or 2 to 4 carbon atoms. In some embodiments, the alkynyl group has one, two, or three carbon-carbon triple bonds. Examples include, but are not limited to -C=CH, -C=CCH3, -CH2C=CCH3, -C=CCH2CH(CH2CH3)2, among others. Representative substituted alkynyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di- or tri-substituted with substituents such as those listed above.

[0091] Aryl groups are cyclic aromatic hydrocarbons that do not contain heteroatoms. Aryl groups herein include monocyclic, bicyclic, and tricyclic ring systems. Aryl groups may be substituted or unsubstituted. Thus, aryl groups include, but are not limited to, phenyl, azulenyl, heptalenyl, biphenyl, fluorenyl, phenanthrenyl, anthracenyl, indenyl, indanyl, pentalenyl, and naphthyl groups. In some embodiments, aryl groups contain 6-14 carbons, and in others from 6 to 12 or even 6-10 carbon atoms in the ring portions of the groups. In some embodiments, the aryl groups are phenyl or naphthyl. The phrase “aryl groups” includes groups containing fused rings, such as fused aromatic-aliphatic ring systems (e.g., indanyl, tetrahydronaphthyl, and the like). Representative substituted aryl groups may be mono-substituted (e.g., tolyl) or substituted more than once. For example, monosubstituted aryl groups include, but are not limited to, 2-, 3-,4-, 5-, or 6-substituted phenyl or naphthyl groups, which may be substituted with substituents such as those listed above.

[0092] Aralkyl groups are alkyl groups as defined above in which a hydrogen or carbon bond of an alkyl group is replaced with a bond to an aryl group as defined above. Aralkyl groups may be substituted or unsubstituted. In some embodiments, aralkyl groups contain 7 to 16 carbon atoms, 7 to 14 carbon atoms, or 7 to 10 carbon atoms. Substituted aralkyl groups may be substituted at the alkyl, the aryl or both the alkyl and aryl portions of the group. Representative aralkyl groups include but are not limited to benzyl and phenethyl groups and fused (cycloalkylaryl)alkyl groups such as 4-indanylethyl. Representative substituted aralkyl groups may be substituted one or more times with substituents such as those listed above.

[0093] Heterocyclyl groups include aromatic (also referred to as heteroaryl) and nonaromatic ring compounds containing 3 or more ring members, of which one or more is a heteroatom such as, but not limited to, N, O, and S. Heterocyclyl groups may be substituted or unsubstituted. In some embodiments, the heterocyclyl group contains 1, 2, 3 or 4 heteroatoms. In some embodiments, heterocyclyl groups include mono-, bi- and tricyclic rings having 3 to 16 ring members, whereas other such groups have 3 to 6, 3 to 10, 3 to 12, or 3 to 14 ring members. Heterocyclyl groups encompass aromatic, partially unsaturated and saturated ring systems, such as, for example, imidazolyl, imidazolinyl and imidazolidinyl groups. The phrase “heterocyclyl group” includes fused ring species including those comprising fused aromatic and non-aromatic groups, such as, for example, benzotriazolyl, 2,3-dihydrobenzo[l,4]dioxinyl, andbenzofl, 3]dioxolyl. The phrase also includes bridged polycyclic ring systems containing a heteroatom such as, but not limited to, quinuclidyl. The phrase includes heterocyclyl groups that have other groups, such as alkyl, oxo or halo groups, bonded to one of the ring members, referred to as “substituted heterocyclyl groups.” Heterocyclyl groups include, but are not limited to, aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydrofuranyl, dioxolyl, furanyl, thiophenyl, pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, piperidyl, piperazinyl, morpholinyl,thiomorpholinyl, tetrahydropyranyl, tetrahydrothiopyranyl, oxathiane, dioxyl, dithianyl, pyranyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, dihydropyridyl, dihydrodithiinyl, dihydrodithionyl, homopiperazinyl, quinuclidyl, indolyl, indolinyl, isoindolyl,azaindolyl (pyrrolopyridyl), indazolyl, indolizinyl, benzotriazolyl, benzimidazolyl, benzofuranyl, benzothiophenyl, benzthiazolyl, benzoxadiazolyl, benzoxazinyl, benzodithiinyl, benzoxathiinyl, benzothiazinyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[l,3]dioxolyl, pyrazolopyridyl, imidazopyridyl (azabenzimidazolyl), triazolopyridyl, isoxazolopyridyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, quinolizinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl, pteridinyl, thianaphthyl, dihydrobenzothiazinyl, dihydrobenzofuranyl, dihydroindolyl, dihydrobenzodioxinyl, tetrahydroindolyl, tetrahydroindazolyl, tetrahydrobenzimidazolyl, tetrahydrobenzotriazolyl,tetrahydropyrrol opyridyl, tetrahydropyrazolopyridyl, tetrahydroimidazopyridyl, tetrahydrotriazolopyridyl, and tetrahydroquinolinyl groups. Representative substituted heterocyclyl groups may be mono-substituted or substituted more than once, such as, but not limited to, pyridyl or morpholinyl groups, which are 2-, 3-, 4-, 5-, or 6-substituted, or disubstituted with various substituents such as those listed above.

[0094] Heteroaryl groups are aromatic ring compounds containing 5 or more ring members, of which, one or more is a heteroatom such as, but not limited to, N, O, and S. Heteroaryl groups may be substituted or unsubstituted. Heteroaryl groups include, but are not limited to, groups such as pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, benzothiophenyl, furanyl, benzofuranyl, indolyl, azaindolyl (pyrrolopyridinyl), indazolyl, benzimidazolyl, imidazopyridinyl (azabenzimidazolyl), pyrazolopyridinyl, triazolopyridinyl, benzotriazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thianaphthyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl groups. Heteroaryl groups include fused ring compounds in which all rings are aromatic such as indolyl groups and include fused ring compounds in which only one of the rings is aromatic, such as 2,3-dihydro indolyl groups. Representative substituted heteroaryl groups may be substituted one or more times with various substituents such as those listed above.

[0095] Heterocyclylalkyl groups are alkyl groups as defined above in which a hydrogen or carbon bond of an alkyl group is replaced with a bond to a heterocyclyl group as defined above. Heterocyclylalkyl groups may be substituted or unsubstituted. Substituted heterocyclylalkyl groups may be substituted at the alkyl, the heterocyclyl or both the alkyl and heterocyclyl portions of the group. Representative heterocyclyl alkyl groups include, but are not limited to, morpholin-4-yl-ethyl, furan-2-yl-methyl, imidazol-4-yl-methyl, pyridin-3-yl-methyl, tetrahydrofuran-2-yl-ethyl, and indol-2-yl-propyl. Representative substituted heterocyclylalkyl groups may be substituted one or more times with substituents such as those listed above.

[0096] Heteroaralkyl groups are alkyl groups as defined above in which a hydrogen or carbon bond of an alkyl group is replaced with a bond to a heteroaryl group as defined above. Heteroaralkyl groups may be substituted or unsubstituted. Substituted heteroaralkyl groups may be substituted at the alkyl, the heteroaryl or both the alkyl and heteroaryl portions of the group. Representative substituted heteroaralkyl groups may be substituted one or more times with substituents such as those listed above.

[0097] Groups described herein having two or more points of attachment (i.e., divalent, trivalent, or polyvalent) within the compound of the present technology are designated by use of the suffix, “ene.” For example, divalent alkyl groups are alkylene groups, divalent aryl groups are arylene groups, divalent heteroaryl groups are divalent heteroarylene groups, and so forth. Substituted groups having a single point of attachment to the compound of the present technology are not referred to using the “ene” designation. Thus, e.g., chloroethyl is not referred to herein as chloroethylene.

[0098] Alkoxy groups are hydroxyl groups (-OH) in which the bond to the hydrogen atom is replaced by a bond to a carbon atom of a substituted or unsubstituted alkyl group as defined above. Alkoxy groups may be substituted or unsubstituted. Examples of linear alkoxy groups include but are not limited to methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, and the like. Examples of branched alkoxy groups include but are not limited to isopropoxy, sec-butoxy, tertbutoxy, isopentoxy, isohexoxy, and the like. Examples of cycloalkoxy groups include but are not limited to cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and the like.Representative substituted alkoxy groups may be substituted one or more times with substituents such as those listed above.

[0099] The terms “alkanoyl” and “alkanoyloxy” as used herein can refer, respectively, to -C(O)-alkyl groups and -O-C(O)-alkyl groups, each containing 2-5 carbon atoms. Similarly, “aryloyl” and “aryloyloxy” refer to -C(O)-aryl groups and -O-C(O)-aryl groups.

[0100] The terms "aryloxy" and “arylalkoxy” refer to, respectively, a substituted or unsubstituted aryl group bonded to an oxygen atom and a substituted or unsubstituted aralkyl group bonded to the oxygen atom at the alkyl. Examples include but are not limited to phenoxy, naphthyloxy, and benzyloxy. Representative substituted aryloxy and arylalkoxy groups may be substituted one or more times with substituents such as those listed above.

[0101] The term “carboxylate” as used herein refers to a -COOH group.

[0102] The term “ester” as used herein refers to -COOR70and -C(O)O-G groups. R70is a substituted or unsubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heterocyclylalkyl or heterocyclyl group as defined herein. G is a carboxylate protecting group. Carboxylate protecting groups are well known to one of ordinary skill in the art. An extensive list of protecting groups for the carboxylate group functionality may be found in Protective Groups in Organic Synthesis, Greene, T. W.; Wuts, P. G. M., John Wiley & Sons, New York, NY, (3rd Edition, 1999) which can be added or removed using the procedures set forth therein and which is hereby incorporated by reference in its entirety and for any and all purposes as if fully set forth herein.

[0103] The term “amide” (or “amido”) includes C- and N-amide groups, i.e., -C(O)NR71R72, and -NR71C(O)R72groups, respectively. R71and R72are independently hydrogen, or a substituted or un substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl or heterocyclyl group as defined herein. Amido groups therefore include but are not limited to carbamoyl groups (-C(O)NH2) and formamide groups (-NHC(O)H). In some embodiments, the amide is -NR71C(O)-(CI-5 alkyl) and the group is termed "carbonylamino," and in others the amide is -NHC(O)-alkyl and the group is termed "alkanoylamino."

[0104] The term “nitrile” or “cyano” as used herein refers to the -CN group.

[0105] Urethane groups include N- and O-urethane groups, i.e., -NR73C(O)OR74and -OC(O)NR73R74groups, respectively. R73and R74are independently a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, or heterocyclyl group as defined herein. R73may also be H.

[0106] The term “amine” (or “amino”) as used herein refers to -NR75R76groups, wherein R73and R76are independently hydrogen, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl or heterocyclyl group as defined herein. In some embodiments, the amine is alkylamino, dialkylamino, arylamino, or alkylarylamino. In other embodiments, the amine is NH2, methylamino, dimethylamino, ethylamino, diethylamino, propylamino, isopropylamino, phenylamino, or benzylamino.

[0107] The term “sulfonamido” includes S- and N-sulfonamide groups, i.e., -SO2NR78R79and -NR78SC>2R79groups, respectively. R78and R79are independently hydrogen, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, or heterocyclyl group as defined herein. Sulfonamido groups therefore include but are not limited to sulfamoyl groups (-SO2NH2). In some embodiments herein, the sulfonamido is -NHSO2-alkyl and is referred to as the "alkylsulfonylamino" group.

[0108] The term “thiol” refers to -SH groups, while “sulfides” include -SR80groups, “sulfoxides” include -S(O)R81groups, “sulfones” include -SO2R82groups, and “sulfonyls” include -SO2OR83. R80, R81, R82, and R83are each independently a substituted or unsubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl aralkyl, heterocyclyl or heterocyclylalkyl group as defined herein. In some embodiments the sulfide is an alkylthio group, -S-alkyl.

[0109] The term “urea” refers to -NR84-C(O)-NR83R86groups. R84, R85, and R86groups are independently hydrogen, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl group as defined herein.

[0110] The term “amidine” refers to -C(NR87)NR88R89and -NR87C(NR88)R89, wherein R87, R88, and R89are each independently hydrogen, or a substituted or unsubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl aralkyl, heterocyclyl or heterocyclylalkyl group as defined herein.

[0111] The term “guanidine” refers to -NR90C(NR91)NR92R93, wherein R90, R91, R92and R93are each independently hydrogen, or a substituted or unsubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl aralkyl, heterocyclyl or heterocyclylalkyl group as defined herein.

[0112] The term “enamine” refers to -C(R94)=C(R95)NR96R97and -NR94C(R95)=C(R96)R97, wherein R94, R95, R96and R97are each independently hydrogen, a substituted or unsubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl aralkyl, heterocyclyl or heterocyclylalkyl group as defined herein.

[0113] The term “halogen” or “halo” as used herein refers to bromine, chlorine, fluorine, or iodine. In some embodiments, the halogen is fluorine. In other embodiments, the halogen is chlorine or bromine.

[0114] The term “hydroxyl” as used herein can refer to -OH or its ionized form, -O. A “hydroxyalkyl” group is a hydroxyl-substituted alkyl group, such as HO-CH2-.

[0115] The term “imide” refers to -C(O)NR98C(O)R99, wherein R98and R99are each independently hydrogen, or a substituted or unsubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl aralkyl, heterocyclyl or heterocyclylalkyl group as defined herein.

[0116] The term “imine” refers to -CR100(NR101) and -N(CR100R101) groups, wherein R100and R101are each independently hydrogen or a substituted or unsubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl aralkyl, heterocyclyl or heterocyclylalkyl group as defined herein, with the proviso that R100and R101are not both simultaneously hydrogen.

[0117] The term “nitro” as used herein refers to an -NO2 group.

[0118] The term “trifluoromethyl” as used herein refers to -CF3.

[0119] The term “trifluoromethoxy” as used herein refers to -OCF3.

[0120] The term “azido” refers to -N3.

[0121] The term “trialkyl ammonium” refers to a -N(alkyl)3 group. A trialkylammonium group is positively charged and thus typically has an associated anion, such as halogen anion.[00122J The term “isocyano” refers to -NC.

[0123] The term “isothiocyano” refers to -NCS.

[0124] The term “pentafluorosulfanyl” refers to -SFs.

[0125] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 atoms refers to groups having 1, 2, or 3 atoms. Similarly, a group having 1-5 atoms refers to groups having 1, 2, 3, 4, or 5 atoms, and so forth.Single-Walled Carbon Nanotubes (SWCNTs)

[0126] Described herein are devices and methods comprising single-walled carbon nanotubes (SWCNTs). SWCNTs are rolled sheets of graphene with nanometer-sized diameters. SWCNTs are defined by their chirality. The sheets that make up the SWCNTs are rolled at specific and discrete, i.e., “chiral” angles. This rolling angle in combination with the nanotube radius determines the nanotube's properties. SWCNTs of different chiralities have different electronical properties. These electronic properties are correlated with respective differences in optical properties. Thus, individually-dispersed semiconducting SWCNTs exhibit ideal qualities as optical biomedical sensors.

[0127] Semiconducting SWCNTs are fluorescent in the near-infrared (NIR, 900-1600 nm) due to their electronic band-gap between valence and conduction band. The semiconducting forms of SWCNTs, when dispersed by surfactants in aqueous solution, can display distinctive near-infrared (IR) photoluminescence arising from their electronic band gap. IR is a wavelength range penetrant to tissue, and thus potentially suitable for implantable sensors or other devices. The band-gap energy is sensitive to the local dielectric environment around the SWCNT, and this property can be exploited in chemical sensing.

[0128] The lowest energy transition, denoted as the En transition, relates to photoluminescence (PL) generated by a radiative recombination process of the exciton, which is a quasi-particle state of an excited electron and the corresponding hole. A significant drawback of SWCNT PL is their very low photoluminescence quantum yield (PLQY), which is caused by the quenching processes of mobile excitons in SWCNTs such as tube edge collision and low-lying exciton states. The capturing of the mobile excitons and their efficient conversion to PL has been achieved by limited chemical functionalization, namely local chemical functionalization (If). This functionalization allows local sp3carbon defects to be doped into the crystalline sp2 carbon network structures of SWCNTs through chemical bond formation with modifier molecules such as aryldiazonium salts and alkyl halides. The locally functionalized SWCNTs (If-SWCNTs) newly show defect PL with longer wavelengths and higher PLQYs compared to that of the En PL from pristine SWCNTs. Typically, chiral (6,5)-rich SWCNTs are used. The defect photoluminescence (PL) from locally functionalized SWCNTs (If-SWCNTs) with (6,5) chirality has been mainly observed in the 1100-1200 nm region for En* PL and to a limited extent in the >1200 nm region for En*- PL, also denoted as En** PL, respectively.Functionalized SWCNTs, Systems, Devices, and Methods of the Present Technology

[0129] In one aspect, the present disclosure provides a functionalized single-walled carbon nanotube (SWCNT) that (a) is covalently functionalized with a plurality of molecules and (b) exhibits luminescent sp3defects, wherein the functionalized SWCNT is para-functionalized and / or ortho-functionalized, wherein the plurality of molecules that are covalently functionalizedcomprise one or more functional groups selected from among a boronic acid group, a carboxyl group, a hydroxyl group, an ester group, an amino group, an amide group, an aldehyde group, a ketone group, an ether group, an acrylate group, an acrylamide group, and a styrene group, and wherein the plurality of molecules that are covalently functionalized are derived from and / or comprise one or more of alcohols, amines, amides, aldehydes, ketones, amino acids, carboxylic acids, acrylate monomers, acrylamide monomers, substituted alkyls, unsubstituted alkyls, heteroaromatics, substituted aryls, unsubstituted aryls, sugars, or styrene monomers. The plurality of molecules may comprise a nucleic acid, a peptide, or a protein. In certain embodiments, the functionalized SWCNT is a (6,5) SWCNT, a (7, 3) SWCNT, a (7, 5) SWCNT, or a (8, 4) SWCNT.

[0130] In some embodiments, the functionalized SWCNT is not encapsulated with a polymer or a surfactant. In other embodiments, the functionalized SWCNT is encapsulated with a polymer or a surfactant, and the plurality of molecules is not conjugated to the polymer or the surfactant. Examples of polymers include DNA (e.g, single stranded DNA (ssDNA)), LNAs, PNAs, peptides, proteins, polyfluorene, polycarbazole, aryleneethynylene polymers, polyethylene glycol (PEG) derivatives, or dextran-based polymers. Examples of surfactants include Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SUS), Sodium n-tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n-octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC). The polymer may be conjugated to the functionalized SWCNT directly or via a linker. In some embodiments, the linker comprises a 6 carbon (C6) linker, polyethylene glycol (PEG), a hydrocarbon, a synthetic polymer, or a biopolymer.

[0131] Additionally or alternatively, in some embodiments of the functionalized SWCNTs disclosed herein, the alcohols are primary alcohols, secondary alcohols, or tertiary alcohols. Examples of suitable alcohols include, but are not limited to, 1, 2, 4-butanetriol, 1, 2-propanediol, 1, 3-propanediol, 1, 4-butanediol, 1-butanol, 2-butanol, 4,4,4-Trifluoro-l -butanol, 1 -hexanol, 1 -pentanol, 1 -propanol, 2 -m ethyl- 1 -propanol, 2-propanol, 2-fluoropropan-l-ol, 3-fluoro-1 -propanol, l,3-difluoro-2-propanol, 2,2-difluoro-l -propanol, 3, 3 -difluoro- 1 -propanol, 3,3,3-trifluoro-l-propanol, l,l,l-trifluoro-2-propanol, 2,2,2-trifluoroethanol, 2,2-difluoroethanol, 2,2-dimethylpropan-l-ol, 2-hydroxymethyl-l,3-propanediol, 2-fluoroethanol, ethanol, methanol, phenol, and tert-butanol. Additionally or alternatively, in certain embodiments of the functionalized SWCNTs disclosed herein, the amines are primary amines, secondary amines, tertiary amines, aliphatic amines, or aromatic amines. Examples of suitable amines include 1, 2-diaminoethane, tert-butyl amine, pentane- 1,5-diamine dihydrochloride, propylamine hydrochloride, and triethylamine hydrochloride, among others. Additionally or alternatively, in some embodiments of the functionalized SWCNTs disclosed herein, the amino acids are naturally occurring amino acids, unnatural amino acids, L-amino acids (e.g., L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-carnosine, L-cysteine, L-glutamine, L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine, L-valine, fmoc-L-alanine, L-glutamic acid, L-tert-leucine, L-leucine methyl ester hydrochloride), or D-amino acids. Examples of suitable amino acids include, but are not limited to, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, norvaline (e.g., DL-norvaline), phenylalanine, proline, sarcosine (N-methylglycine), serine, threonine, tryptophan, tyrosine, and valine. In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the carboxylic acids are primary carboxylic acids, secondary carboxylic acids, tertiary carboxylic acids, aliphatic carboxylic acids, or aromatic carboxylic acids. Examples of suitable carboxylic acids include, but are not limited to, acetic acid, acrylic acid, Methacrylic acid, 3,3-Dimethyl acrylic acid, trifluoroacetic acid, propionic acid, 2,2-difluoropropionic acid, 3,3,3-trifluoropropionic acid, crotonic acid, butyric acid, 2-aminobutyric acid, isobutyric acid, 3-hydroxypropionic acid, lactic acid, sodium pyruvate, glutaric acid, succinic acid disodium salt, mesaconic acid, fumaric acid, angelic acid, tiglic acid, itaconic acid, trans-cinnamic acid, and pivalic acid. In some embodiments, the acrylamide monomers are selected from among acrylamide, N, N-methylenebisacrylamide, 2-acrylamido-2-methylpropane sulfonic acid, 3-(acrylamido)phenylboronic acid, N-isopropylacrylamide, and n-tert-butyl acrylamide. In certain embodiments, the acrylate monomers are selected from among acrylic acid, methylacrylic acid,methacrylic acid, acryloxyethyl thiocarbamoyl rhodamine, 2, 2, 2, -trifluoroethyl methacrylate, and bis[2-(methacryloyloxy)ethyl] phosphate.[00132J In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the boronic acids (alkyl or aryl boronic acids) may include 4-biphenylboronic acid, boric acid, butylboronic acid, 4-tert-butylphenyl boronic acid, 4-carboxyphenylboronic acid, 4-(diethylamino)phenylboronic acid, 4-ethoxyphenyl boronic acid, ethylboronic acid, 3-fluorophenylboronic acid, 4-fluorophenylboronic acid, hexylboronic acid, 4-hydroxyphenyl boronic acid, 4-(methanesulfonyl)phenylboronic acid, 4-methoxyphenyl boronic acid, methylboronic acid. In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the esters may include n-butyl acetate, ethyl acetate, and propyl acetate. In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the ethers may include methyl tert-butyl ether.

[0133] In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the amides may include acetamide, propionamide, N, N-dimethylacetamide, ethyl acetamide, methyl acetamide, acrylamide, N-methacrylamide, N-ethylacrylamide, N-isopropyl acrylamide (NIP AM), N, N’ -methylenebisacrylamide, N-tert-butylacrylamide, N-phenylacrylamide, diacetone acrylamide, 2-acrylamido-2-methylpropane sulfonic acid, N-(2-Aminoethyl) methacrylamide hydrochloride, and N-(3 -aminopropyl) methacrylamide hydrochloride. In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the aldehydes may include acetaldehyde, and propionaldehyde. In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the ketones may include acetone, 2-butanone, 3-penten-2-one, 1,3 -difluoroacetone, acetylacetone, 3,3-dimethyl-2-butanone, and hydroxy acetone.

[0134] In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the aromatic molecules may include 7-azaindole, benzoic acid, l-(3-hydroxypropyl)pyrrole, imidazole, indole, 3 -methyladenine, 1-naphthol, 2-(l-naphthyl)ethanol, phenol, phenylphosphonic acid, 2-picolinic acid, piperazine, purine, pyrazine, pyridazine, 4-pyridinylboronic acid, pyrimidine, 4-pyrimidinecarboxylic acid, 5-pyrimidylboronic acid, toluene, and vanillic acid.[00135J In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, the sugars may include L -Fucose. In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, target molecules (also referred herein as molecules of interest) for functionalization may include sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, sodium deoxycholate, poly(N-isopropylacrylamide), maleimide, biotin, adenine, cytosine, guanine, thymine, uracil, dimethyl sulfoxide, lipoic acid, methanesulfonic acid, and ethanesulfonic acid, among others.

[0136] In any of the preceding embodiments of the functionalized SWCNTs disclosed herein, monomers for functionalizing SWCNTs may include acrylic acid, acrylates, acrylamides, esters (e.g., n-butyl acetate, ethyl acetate, and propyl acetate), and amides (e.g., acetamide, propionamide, N, N-dimethylacetamide, ethyl acetamide, methyl acetamide, acrylamide, N-Methacrylamide, N-Ethyl acrylamide, N-Isopropylacrylamide (NIP AM), N, N’-Methylenebisacrylamide, N-tert-Butyl acrylamide, N-Phenyl acrylamide, diacetone acrylamide, 2-acrylamido-2-methylpropane sulfonic acid, N-(2 -Aminoethyl) methacrylamide hydrochloride, and N-(3 -aminopropyl) methacrylamide hydrochloride), among others.

[0137] In any and all embodiments of the functionalized SWCNTs disclosed herein, the functionalized SWCNT exhibits a detectable change in intrinsic fluorescence relative to a native SWCNT’s El 1 emission peak.

[0138] In one aspect, the present disclosure provides a SWCNT sensor comprising any and all embodiments of at least one functionalized SWCNT described herein.

[0139] In another aspect, the present disclosure provides a device comprising any and all embodiments of the at least one SWCNT sensor disclosed herein and a solid support on which the device is immobilized. The solid support may comprise a biocompatible gel, a microcapillary, a fdter, a mesh, a tubing, a compartment / dialysis membrane, or a combination thereof. In some embodiments, the device comprises a microfluidic chamber containing the at least one SWCNT sensor, wherein the at least one SWCNT sensor is immobilized on a surface orcontained in a semi-permeable enclosure. In some embodiments, the device is a sensor, or comprises a sensor, as described herein, and is a device for a non-medical application. In certain embodiments, the device is a device for monitoring environmental conditions.

[0140] In some embodiments, the SWCNT sensor may be used for single photon emission applications. When used for single-photon emission applications, the SWCNT sensor may radiate or emit one photon or single particles at a given time. The radiation of photons or particles from the SWCNT sensor may be controlled, such that a single photon or particle is transmitted over the given time. In some embodiments, the single photon emission by the SWCNT sensor may be in accordance with photon anti-bunching. For example, the SWCNT sensor may emit single photons or particles in a sequential manner, as opposed to a grouped manner. This may be measured by the second-order correlation of the light emitted by the SWCNT being substantially zero (e.g., within 10%). The single photon emission applications may include, for example, single-photon emission imaging (e.g., single-photon emission computed tomography (SPECT), light detection and ranging (LiDAR), and quantum imaging) and quantum computing (e.g., quantum cryptography, quantum key distribution (QKD), quantum communication, and quantum information processing), among others.

[0141] In one aspect, the present disclosure provides a system comprising any and all embodiments of the device described herein, an excitation light source; and a detector for detecting light emitted from the at least one SWCNT sensor in the device following excitation by the excitation light source. In some embodiments of the system disclosed herein, the device comprises a biocompatible gel, a microcapillary, a filter, a mesh, a tubing, a compartment / dialysis membrane, and / or a solid support on or in which the at least one SWCNT sensor is immobilized. In certain embodiments, the excitation light source emits near-infrared light or light having a wavelength greater than 700 nm. Additionally or alternatively, in some embodiments of the system described herein, the detector detects fluorescent light. The device may be shaped and sized for subcutaneous, intraperitoneal, intrauterine, or intravenous implantation, or for delivery via injection. In any and all embodiments of the system describedherein, the detector and the excitation light source are part of a unit. The unit may comprise a handheld unit positioned outside the subject or within a body cavity of the subject.[00142J Additionally or alternatively, in some embodiments of the system described herein, the device is configured for attachment to or embedding within a wall of a body cavity, lumen, or organ. The body cavity, lumen, or organ may comprise a member selected from the group consisting of uterine cavity, cranial cavity, vertebral canal, thoracic cavity, abdominal cavity, pelvic cavity, artery, vein, gastrointestinal tract, bronchi, renal tubules, urinary collecting ducts, vagina, uterus, fallopian tubes, adrenal gland, bone, esophagus, heart, larynx, mouth, pituitary gland, muscle, spleen, thyroid, anus, brain, eye, hypothalamus, liver, nose, prostate, skin, stomach, ureter, appendix, gall bladder, kidney, lung, pancreas, rectum, small intestine, thymus, urethra, bladder, ear, genitals, large intestine, lymph node, parathyroid gland, salivary gland, spinal cord, and trachea.

[0143] In another aspect, the present disclosure provides a kit comprising any and all embodiments of the functionalized SWCNT or the SWCNT sensor described herein, at least one container and instructions for use. The at least one container may be an ampule, a vial, a cartridge, a reservoir, a lyo-ject, or a pre- filled syringe.

[0144] In one aspect, the present disclosure provides a method for preparing functionalized SWCNTs comprising: incubating a plurality of native SWCNTs with a plurality of molecules in the presence of a Fenton-like metal and hydrogen peroxide under conditions that permit covalent attachment of the plurality of molecules to the native SWCNTs, wherein the plurality of molecules are selected from among alcohols, amines, amino acids, carboxylic acids, acrylate monomers, acrylamide monomers, alkyls, heteroaromatics, aryls, and styrene monomers. In some embodiments, the Fenton-like metal is Fe, Mn, Ce, Cu, Ag, or Mn. Additionally or alternatively, in some embodiments of the methods disclosed herein, the Fenton-like metal is derived from FeBn, Feb, ferrocene, ferrocene-derivatives (e.g. ferrocene carboxylic acid), iron(II) trifluoromethane sulfonic acid, FeCh, or Fe(III) tosylate.

[0145] Additionally or alternatively, in certain embodiments, the Fenton-like metal is present in a concentration that ranges from about 10 nM to about 35 pM. In some embodiments, theFenton-like metal is present in a concentration of about 10 nM, about 12 nM, about 14 nM, about 16 nM, about 18 nM, about 20 nM, about 22 nM, about 24 nM, about 26 nM, about 28 nM, about 30 nM, about 32 nM, about 34 nM, about 36 nM, about 38 nM, about 40 nM, about 42 nM, about 44 nM, about 46 nM, about 48 nM, about 50 nM, about 52 nM, about 54 nM, about 56 nM, about 58 nM, about 60 nM, about 62 nM, about 64 nM, about 66 nM, about 68 nM, about 70 nM, about 72 nM, about 74 nM, about 76 nM, about 78 nM, about 80 nM, about 82 nM, about 84 nM, about 86 nM, about 88 nM, about 90 nM, about 92 nM, about 94 nM, about 96 nM, about 98 nM, about 100 nM, about 125 nM, about 150 nM, about 175 nM, about 200 nM, about 225 nM, about 250 nM, about 275 nM, about 300 nM, about 325 nM, about 350 nM, about 375 nM, about 400 nM, about 425 nM, about 450 nM, about 475 nM, about 500 nM, about 525 nM, about 550 nM, about 575 nM, about 600 nM, about 625 nM, about 650 nM, about 675 nM, about 700 nM, about 725 nM, about 750 nM, about 775 nM, about 800 nM, about 825 nM, about 850 nM, about 875 nM, about 900 nM, about 925 nM, about 950 nM, about 975 nM, about 1 pM, about 2 pM, about 3 pM, about 4 pM, about 5 pM, about 6 pM, about 7 pM, about 8 pM, about 9 pM, about 10 pM, about 11 pM, about 12 pM, about 13 pM, about 14 pM, about 15 pM, about 16 pM, about 17 pM, about 18 pM, about 19 pM, about 20 pM, about 21 pM, about 22 pM, about 23 pM, about 24 pM, about 25 pM, about 26 pM, about 27 pM, about 28 pM, about 29 pM, about 30 pM, about 31 pM, about 32 pM, about 33 pM, about 34 pM, or about 35 pM.

[0146] Additionally or alternatively, in some embodiments, the plurality of native SWCNTs are incubated with the plurality of molecules for about 5 minutes to about 12 hours. In certain embodiments, the plurality of native SWCNTs are incubated with the plurality of molecules for about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, about 1 hr, about 1.25 hrs, about 1.5 hrs, about 1.75 hrs, about 2 hrs, about 2.25 hrs, about 2.5 hrs, about 2.75 hrs, about 3 hrs, about 3.25 hrs, about 3.5 hrs, about 3.75 hrs, about 4 hrs, about 4.25 hrs, about 4.5 hrs, about 4.75 hrs, about 5 hrs, about 5.25 hrs, about 5.5 hrs, about 5.75 hrs, about 6 hrs, about 6.25 hrs, about 6.5 hrs, about 6.75 hrs, about 7 hrs, about 7.25 hrs, about 7.5 hrs, about 7.75 hrs, about 8 hrs, about 8.25 hrs, about 8.5 hrs, about 8.75 hrs, about 9hrs, about 9.25 hrs, about 9.5 hrs, about 9.75 hrs, about 10 hrs, about 10.25 hrs, about 10.5 hrs, about 10.75 hrs, about 11 hrs, about 11.25 hrs, about 11.5 hrs, about 11.75 hrs, or about 12 hrs.[00147J In any of the preceding embodiments, the method further comprises encapsulating the plurality of native SWCNTs with a polymer or a surfactant, wherein the plurality of molecules are not conjugated to the polymer or the surfactant. Examples of polymers include DNA (e.., single stranded DNA (ssDNA)), LNAs, PNAs, peptides, proteins, polyfluorene, polycarbazole, aryleneethynylene polymers, polyethylene glycol (PEG) derivatives, or dextran-based polymers. Examples of surfactants include Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SETS), Sodium n-tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n-octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC). Alternatively, in some embodiments, the plurality of native SWCNTs or the functionalized SWCNTs are not encapsulated with a polymer or a surfactant.

[0148] In one aspect, the present disclosure provides a method for preparing functionalized SWCNTs comprising: incubating a plurality of native SWCNTs with a plurality of molecules in the presence of heat and hydrogen peroxide under conditions that permit covalent attachment of the plurality of molecules to the native SWCNTs, wherein the plurality of molecules are selected from among alcohols, amines, amino acids, carboxylic acids, alkyls, heteroaromatics, aryls, acrylate monomers, acrylamide monomers, and styrene monomers. In certain embodiments, the plurality of native SWCNTs are incubated with the plurality of molecules for about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, or about 35 minutes.

[0149] In some embodiments, the plurality of native SWCNTs are heated to a temperature ranging from about 22°C- about 60°C. In certain embodiments, the plurality of native SWCNTs are heated to a temperature of about 22°C, about 23°C, about 24°C, about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, about 30°C, about 31°C, about 32°C, about 33°C, about 34°C, about 35°C, about 36°C, about 37°C, about 38°C, about 39°C, about 40°C, about 41°C, about 42°C, about 43°C, about 44°C, about 45°C, about 46°C, about 47°C, about 48°C, about49°C, about 50°C, about 51°C, about 52°C, about 53°C, about 54°C, about 55°C, about 56°C, about 57°C, about 58°C, about 59°C, or about 60°C.[00150J In any of the preceding embodiments, the method further comprises encapsulating the plurality of native SWCNTs with a polymer or a surfactant, wherein the plurality of molecules are not conjugated to the polymer or the surfactant. Examples of polymers include DNA (e.., single stranded DNA (ssDNA)), LNAs, PNAs, peptides, proteins, polyfluorene, polycarbazole, aryleneethynylene polymers, polyethylene glycol (PEG) derivatives, or dextran-based polymers. Examples of surfactants include Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SETS), Sodium n-tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n-octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC). Alternatively, in some embodiments, the plurality of native SWCNTs or the functionalized SWCNTs are not encapsulated with a polymer or a surfactant.

[0151] Additionally or alternatively, in some embodiments of the methods disclosed herein, the alcohols are primary alcohols, secondary alcohols, or tertiary alcohols. Examples of suitable alcohols include, but are not limited to, 1, 2, 4-butanetriol, 1, 2-propanediol, 1, 3 -propanediol, 1, 4-butanediol, 1 -butanol, 1 -hexanol, 1 -pentanol, 1 -propanol, 2 -m ethyl- 1 -propanol, 2-propanol, ethanol, methanol, phenol, and tert-butanol. Additionally or alternatively, in certain embodiments of the methods disclosed herein, the amines are primary amines, secondary amines, tertiary amines, aliphatic amines, or aromatic amines. Examples of suitable amines include 1, 2-diaminoethane, and tert-butyl amine. Additionally or alternatively, in some embodiments of the methods disclosed herein, the amino acids are naturally occurring amino acids, unnatural amino acids, L-amino acids, or D-amino acids. Examples of suitable amino acids include, but are not limited to, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. In any of the preceding embodiments of the methods disclosed herein, the carboxylic acids are primary carboxylic acids, secondary carboxylic acids, tertiary carboxylic acids, aliphatic carboxylic acids, or aromatic carboxylic acids. Examples ofsuitable carboxylic acids include, but are not limited to, acetic acid, propionic acid, crotonic acid, and pivalic acid. In some embodiments, the acrylamide monomers are selected from among acrylamide, N, N-methylenebisacrylamide, 2-acrylamido-2-methylpropane sulfonic acid, 3-(acrylamido)phenylboronic acid, N-isopropylacrylamide, and n-tert-butylacrylamide. In certain embodiments, the acrylate monomers are selected from among acrylic acid, methylacrylic acid, methacrylic acid, acryloxyethyl thiocarbamoyl rhodamine, 2, 2, 2, -trifluoroethyl methacrylate, and bis[2-(methacryloyloxy)ethyl] phosphate.

[0152] In any and all embodiments of the methods disclosed herein, the plurality of native SWCNTs are incubated with the plurality of molecules in the presence of UV or light irradiation.

[0153] The SWCNT sensors or devices of the present technology may be used in a variety of applications such as near-infrared single-photon emitters at room temperature, in electroluminescent devices as versatile optical sensors, and as fluorophores for bioimaging and potential super-resolution microscopy. In certain embodiments, the device is a sensing platform.

[0154] In one aspect, the present disclosure provides an imaging method comprising contacting any and all embodiments of the SWCNT sensor disclosed herein with a chemical or a biological sample to form a mixture; exposing the mixture to excitation light; and detecting light emitted by the at least one SWCNT sensor in the mixture following excitation by the excitation light. In another aspect, the present disclosure provides an imaging method comprising administering any and all embodiments of the SWCNT sensor disclosed herein to a subject; exposing the subject to excitation light; and detecting light emitted by the at least one SWCNT sensor in the subject following excitation by the excitation light. In certain embodiments of the methods, the detecting comprises obtaining images of cells or tissue of the biological sample or the subject.

[0155] Also disclosed herein are methods for detecting an analyte in a biological sample comprising contacting any and all embodiments of the SWCNT sensor described herein with a biological sample to form a mixture; exposing the mixture to excitation light; and detecting a wavelength shift in emission electromagnetic radiation (EMR) and / or an intensity shift and / or another change in the spectral characteristics of emission EMR, whereupon reaction of theanalyte with the plurality of molecules present on the functionalized SWCNT results in a detectable change in the emission EMR, thereby identifying the presence of the analyte.[00156J In some embodiments, the device is a sensor, or comprises a sensor, as described herein, and is exposed excitation electromagnetic radiation (excitation EMR) to produce an emission of electromagnetic radiation (emission EMR) by the SWCNT sensor. In certain embodiments, the excitation EMR is ultraviolet light, infrared light, or near-infrared light (NIR). In other embodiments, the excitation EMR is visible light. In certain embodiments, the excitation EMR has a wavelength between 100 nm and 3000 nm, 200 nm and 2000 nm, between 300 and 1500 nm, or between 500 and 1000 nm. In some embodiments, the emission EMR. is ultraviolet light, infrared light, or near-infrared light (NIR). In certain embodiments, the emission EMR is visible light. In certain embodiments, the emission EMR has a wavelength between 300 nm and 3000 nm, between 400 and 2000 nm, between 500 and 1000 nm, between 600 nm and 1400 nm, or between 700 and 1350 nm.

[0157] In certain embodiments, the methods described herein can be used for diagnostic purposes to diagnose any condition or disease characterized by or associated with an analyte as described herein In certain embodiments, the method comprises contacting a test sample comprising one or more analytes of interest; exposing the test sample to excitation electromagnetic radiation (excitation EMR) to produce an emission of electromagnetic radiation (emission EMR) by the SWCNT sensor; detecting the electromagnetic radiation emitted by the SWCNT sensor; and identifying the presence of the one or more analytes of interest in the test sample based at least in part on the detected emission EMR. Sources of excitation EMR can be any such source known in the art, e.g., a laser, a light emitting diode, or a lamp. Detectors of emission EMR can be any such detector known in the art, e.g., a fluorometer In certain embodiments, the method comprises detecting a wavelength shift e.g., a blue or red shift) in the emission EMR and / or an intensity shift (e.g., amplitude shift), or other changes in the spectral characteristics of in the emission EMR, thereby identifying the presence of the analytes in the test sample.

[0158] In some embodiments, the method comprises detecting an intensity shift between an emission center wavelength (e.g., a peak) of the test sample and an emission center wavelength (e.g., a peak) of a reference sample, wherein the reference sample is devoid of the target analyte In certain embodiments, the emission wavelength shift is between 1 nm and 100 nm, between 2 nm and 100 nm, between 3 and 50 nm, or between 4 and 20 nm. In certain embodiments, the wavelength shift is a color shift, e.g., a redshift or a blueshift.

[0159] The SWCNT sensors or devices of the present technology may be used in a variety of applications such as near-infrared single-photon emitters at room temperature, in electroluminescent devices as versatile optical sensors, and as fluorophores for bioimaging and potential super-resolution microscopy. In certain embodiments, the device is a sensing platform.

[0160] In one aspect, the present disclosure provides an imaging method comprising contacting any and all embodiments of the SWCNT sensor disclosed herein with a chemical or a biological sample to form a mixture; exposing the mixture to excitation light; and detecting light emitted by the at least one SWCNT sensor in the mixture following excitation by the excitation light. Tn another aspect, the present disclosure provides an imaging method comprising administering any and all embodiments of the SWCNT sensor disclosed herein to a subject; exposing the subject to excitation light; and detecting light emitted by the at least one SWCNT sensor in the subject following excitation by the excitation light. In certain embodiments of the methods, the detecting comprises obtaining images of cells or tissue of the biological sample or the subject.

[0161] In one aspect, the present disclosure provides a method of performing single-photon emissions. The method may include providing the SWCNT sensor disclosed herein; exposing the SWCNT sensor to excitation light; and detecting light emitted by the at least one SWCNT sensor in accordance with single-photon emissions. In some embodiments, the method may include performing a quantum computing function using the light emitted by the at least one SWCNT sensor. In some embodiments, the quantum computing function comprises at least one of quantum cryptography, quantum key distribution (QKD), quantum communication, or quantum information processing. In some embodiments, the method may include performingsingle-photon emission imaging using the light emitted by the at least one SWCNT sensor. In some embodiments, the single-photon emission imaging may include at least one of singlephoton emission computed tomography (SPECT), light detection and ranging (LiDAR), or quantum imaging.Targets and Analytes

[0162] Target conditions and diseases that can be diagnosed or otherwise assessed using the devices and methods described herein include, for example, cancers (including tumors), metabolic disease, fetal health condition, kidney disease, organ rejection, hereditary diseases, nervous disease, obesity, and infectious disease. In certain embodiments, the condition or disease is at least in part characterized by a substance, t.e., an analyte.

[0163] In certain embodiments, the analytes that can be detected, imaged, mapped, or quantified using the systems, devices, and methods described herein include peptides, polypeptides, proteins, biologies, biomolecules, biosimilars, aptamers, viruses, drugs, lipids, bacteria, toxins, cells, tumor cells, cancer, antibodies, and antibody fragments EXAMPLES

[0164] The present technology is further illustrated by the following Examples, which should not be construed as limiting in any way.Example 1: Materials and Methods

[0165] Fenton Reactions'. A typical reaction was performed using SG65i SWCNTs (1 mg) in pH 3 phthalate buffer (1 mb, 100 mM) containing FeCh (127 ng, 1 pM). 50 pL ethanol was added, followed by addition of H2O2 (200 pL, 50 % (w / v) in water). The mixture was incubated for 30 min, followed by extensive washing with water and subsequent dispersion in DNA / surf actant / other wrapping agent in order to visualize fluorescence.

[0166] In another example, functionalization with molecules valine and 1 -propanol were performed for 30 min at -20, 4, 22 or 37 °C prior to washing and dispersion. Fluorescence emission spectra of SWCNTs were acquired using a home-built near-infrared fluorescencespectroscopy apparatus consisting of a 577 nm laser, inverted microscope and InGaAs NIR detector. The light path was fed into the back of an inverted IX-71 microscope (Olympus), where it passed through a ><20 NIR objective (Olympus) and illuminated the samples in a 96-well plate. Emission from the SWCNTs were collected through the ×20 objective and passed through a dichroic mirror (875 nm cutoff, Semrock). The light was injected into a Shamrock 303i spectrograph (Andor, Oxford Instruments) with a slit width of 100 pm, which dispersed the emission using an 86 g mm⁻¹ grating with 1.35 μm blaze wavelength. The spectral range was 723-1,694 nm with a resolution of 1.89 nm. The light was collected by an iDus 1.7 pm InGaAs (Andor, Oxford Instruments) with an exposure time of 10 s. An HL-3-CAL-EXT halogen calibration light source (Ocean Optics) was used to correct for wavelength-dependent features in the emission intensity arising from the spectrometer, detector and other optics.

[0167] FeCk can be replaced with other iron containing compounds including, but not limited to: other sources of Fe(II) (e.g. FeBn, Feb, ferrocene and ferrocene-derivatives (e.g. ferrocene carboxylic acid), iron(II) trifluoromethane sulfonic acid), sources of Fe(III) (e.g. FeCk, iron(III) tosylate), and other Fenton-like metals such as Mn, Ce, Cu, Ag, Mn. Ethanol can be replaced with whichever molecule is being conjugated to the nanotube surface, including other alcohols (e.g. propanol, tBuOH, propane- 1,2-diol), amines (e.g. tBuNH2, ethylamine), amino acids (e.g. alanine, threonine, valine), carboxylic acids (e.g. propionic acid, acetic acid).

[0168] The reaction time is typically 30 min, but functionalization has also been observed at timepoints ranging from 5 min to overnight. While it is likely some degree of functionalization exists at earlier time points, the defect density would be lower, thus resulting in less observable fluorescence. Conversely, it is likely that longer reaction times lead to a higher level of functionalization, potentially resulting in over-functionalization and subsequent loss of fluorescence.

[0169] Fenton-metal free functionalization'. These reactions were performed using SG65i SWCNTs (1 mg) in pH 3 phthalate buffer (1 mL, 100 mM). 1-Propanol (25 pL), acrylic acid (25 pL) or 4-nitrophenyl boronic acid (25 mg) were added, followed by heating to 22 °C, 37 °C or 60 °C for 5 min, followed by addition of H2O2 (200 pL, 50 % (w / v) in water). The mixture wasincubated at the previously used temperature for 30 min, followed by extensive washing with water and subsequent dispersion in DNA / surfactant / other wrapping agent in order to visualize fluorescence (in this case sodium deoxy cholate (DOC)).

[0170] DNA wrapped protocol.

[0171] A typical reaction for functionalization of DNA-wrapped SWCNTs was performed as follows. SG65i SWCNTs (1 mg) and ssDNA ((GT)15, (3 mg)) were added to water (1 mL) and probe tip sonicated at 30% amplitude for 1 h. The solution was then centrifuged at 30,000 g for 30 min, and the top 800 pL of the supernatant was collected and dialyzed against water (1 L) for 36 h to remove free DNA. These SWCNTs were diluted in water to a final optical density of 2.0.90 pL of this solution was mixed with a solution of FeC12 in water (10 pL, 0.5 mM) and ethanol (20 pL). H2O2 (20 pL, 50 % (w / v) in water) was added and the solution incubated for 15 min. Sodium deoxy cholate (DOC) (20 pL, 1% (w / v) in water) was then added, and fluorescence was measured.

[0172] In some instances, FeCh was omitted to show the increase in functionalization in the presence of catalytic metal ions. In other instances, ethanol was omitted to show the conjugation of the wrapping polymer (in this case (GT)is) rather than ethanol. In other instances, ethanol is replaced with other molecules for conjugation (e.g. alcohols, amines, carboxylic acids, etc).Example 2; Results

[0173] As shown in FIG. 1, different compounds form either 1150 (ortho) or 1250 (para) sp3defects, either preferentially or specifically. A number of monomers also appear to conjugate to SWCNTs using identical reaction conditions to the other small molecule conjugations. See FIG.1. For the majority of these molecules, they form 1250-emitting defects. Taken together, the methods of the present technology are effective in generating libraries of acrylate or acrylamide monomer-, amino acid-, alcohol-, carboxylic acid-, or amine-conjugated functionalized SWCNTs. Exemplary structures of the carboxylic acid-, amino acid-, alcohol-, or amine-conjugated functionalized SWCNTs are provided in FIGs. 4-7.

[0174] For a given compound, it is possible to exert control over the ratio of 1150: 1250 nm emission via modulation of temperature during functionalization. As shown in FIG. 2-3, higher temperatures favor the formation of 1150 (ortho) sp3defects over 1250 (para) sp3defects.

[0175] FIG. 9 shows plot showing fluorescence spectrum of DNA- wrapped SWCNTs treated with H2O2 in the presence of no additive, FeC12, or FeC12 and ethanol.

[0176] FIGs. 13-22 show emission spectra of CCNTs functionalized with various materials. To prepare, Signis SG65i SWCNTs (CHASM, USA) (1 mg) were added to phthalate buffer (875 pL, pH 3, NIST Standard 10111430, Fisher Scientific). The conjugated molecule was then added (25 pL if liquid, 25 mg if solid), followed by FeC12 in water (100 pL, 1 mM). Hydrogen peroxide (200 pL, 50% (w / v) in water) was then added, the solution was briefly vortexed and incubated for 30 min protected from light (vial open to air in case of gas build up). These mixtures were dispensed into 5 mL syringes fitted with 20 pm polyethylene frits, and the nanotubes washed with water (5 x 5 mL). After washing, the functionalized SWCNTs were collected and suspended in solutions of DOC (1 mL, 1% (w / v) in water) via probe tip sonication at 30% amplitude for 15 min. The solution was then centrifuged at 30,000 g for 30 min, and the top 800 pL of the supernatant was collected. These samples were diluted to an optical density (OD) of 1 with 1% DOC, and fluorescence measurement was performed with an excitation wavelength of 577 nm.

[0177] FIGs. 23 and 24 depict spectra showing the functionalization of SWCNTs with propionic acid or with tert-Butyl alcohol respectively at different iron chloride concentrations.FIG. 25 depicts a Raman spectra of tert-Butyl alcohol functionalized nanotubes prepared at different concentrations of iron chloride. To prepare, Signis SG65i SWCNTs (CHASM, USA) (1 mg) were added to phthalate buffer (875 pL, pH 3, NIST Standard 10111430, Fisher Scientific). t-BuOH or propionic acid were then added (25 pL), followed by FeC12 in water (100 pL, 0.1-200 mM). Hydrogen peroxide (200 pL, 50% (w / v) in water) was then added, the solution was briefly vortexed and incubated for 30 min protected from light (vial open to air in case of gas build up). These mixtures were dispensed into 5 mL syringes fitted with 20 pm polyethylene frits, and the nanotubes washed with water (5 x 5 mL). After washing, thefunctionalized SWCNTs were collected and suspended in solutions of DOC (1 mL, 1% (w / v) in water) via probe tip sonication at 30% amplitude for 15 min. The solution was then centrifuged at 30,000 g for 30 min, and the top 800 pL of the supernatant was collected. These samples were diluted to an optical density (OD) of 1 with 1% DOC, and fluorescence measurement was performed with an excitation wavelength of 577 nm.

[0178] FIG. 26 depicts a spectra of the environmental sensitivity of functionalized nanotubes. To prepare, Signis SG65i SWCNTs (CHASM, USA) (1 mg) were added to phthalate buffer (875 pL, pH 3, NIST Standard 10111430, Fisher Scientific). 1-Propanol was added (25 pL), followed by FeC12 in water (100 pL, 0.1-200 mM). Hydrogen peroxide (200 pL, 50% (w / v) in water) was then added, the solution was briefly vortexed and incubated for 30 min protected from light (vial open to air in case of gas build up). These mixtures were dispensed into 5 mL syringes fitted with 20 pm polyethylene frits, and the nanotubes washed with water (5 x 5 mL).

[0179] The functionalized SWCNTs and single stranded DNA (sequence (GT) 15) (3 mg) were added to water (1 mL) and probe tip sonicated at 30% amplitude for 1 h. The solution was then centrifuged at 30,000 g for 30 min, and the top 800 pL of the supernatant was collected and dialyzed against water (1 L) for 36 h to remove free DNA (Spectra-Por, Float-A-Lyzer, MWCO = 1 MDa) with frequent change of water. 50 pL of this solutions was then mixed with 50 pL of each of the following biomolecules: presepsin (1,000 ng / mL), C-reactive protein (CRP, 1 mg / mL), azurocidin (1,000 ng / mL), water (control), procalcitonin (PCT, 20 ng / mL), leptin (40 ng / mL), interleukin-6 (IL6, 800 pg / mL) or lactic acid (10 mM). The fluorescence spectra were then measured for each solution and changes in fluorescence intensity were noted.Example 3: Application of System with SWCNT Sensors

[0180] Presented herein is a sensor device or sensor array, in which each pixel is covered with ink containing different environmentally sensitive SWCNT sensors. The fluorescence spectrum of each pixel can be measured using a fluorescence microscope, a charge-coupled device (CCD) camera, or other fluorimeter. Upon addition of an analyte, even in complexmedium, such as serum, saliva, or urine, each pixel responds differently to the analyte and media components, pH, polarity change, oxygen level, etc.[00181 J The unique response of the whole array to a particular analyte or mix of analytes represents that analyte’s spectral ‘fingerprint’, which can be used to identify the analyte, pattern, or medical condition. In this way, the array resembles a ‘QR code’, with different analytes generating unique fluorescence patterns. Analysis of array response can be performed by fluorescent microscopy by using a charge-coupled device (CCD) camera, a fiber optical device, a mobile phone camera, or by other techniques familiar to experts in the field.

[0182] A neural network is trained to recognize array responses to specific analytes or physico-chemical change. For example, by training the array using serum samples from patients with ovarian cancer versus serum from healthy donors and patients with other conditions, the sensor can be made to diagnose ovarian cancer.

[0183] This array can serve as a general sensor. A single array with a sufficiently high number of unique pixels can be trained to recognize multiple different conditions. Following addition of a single patient sample, spectral analysis of the array would then predict the probability of the patient having each condition for which the sensor was trained. This could be used for early-stage screening of multiple conditions, with positive results being followed up with further testing.

[0184] Arrays can be prepared via directly printing pre-made ink, wherein different pixels can be composed of different inks. Arrays can be prepared via printing a generic ink mixture on every pixel and then printing additional reagents on top of the pixels to modify the pixel behavior. Multiple inks can be overlaid onto the pixels to increase complexity for anticounterfeiting or to alter or tune the fluorescence response upon addition of analyte.

[0185] In some applications, pixels can be functionalized with specific recognition agents such as antibodies, aptamers, molecularly imprinted polymers, etc. The agents may be physically wrapped or adsorbed onto the nanotubes, or covalently linked or grafted onto the nanotube surface via, for example, radical chemistry or other coupling chemistry, or via incorporation into gels such as microgel or aerogel.

[0186] An array with the SWCNT sensors may be used as an anti-counterfeiting label. Each pixel or group of pixels may have a different fluorescence spectrum. The different fluorescence spectra may be due to differences in nanotube ink composition. The different fluorescence spectra may prevent forgery. Custom ink may be synthesized using additive compounds, which can affect the fluorescence spectrum of each ink. Custom ink may be synthesized by filtering a generic ink formulation through a custom separation column (e.g., nanotubes with specific dimensions or surface treatment pass through).

[0187] The physical form of the array may approximately be micrometer to millimeter-sized dots of fluorescent ink printed onto paper, glass, polymer sheets, fabric, or another two-dimensional substrate. However, the array could also be printed directly onto the bottom of a microtiter plate well, a cell-culture flask, dish, or other liquid-holding receptacle, depending on application.

[0188] The array can be applied for analysis of liquid or gas samples. The array can be applied for single use or for continuous monitoring of analytical samples. The array could also be used for detection of specific molecules of interest, such as drugs, explosives, and environmental pollutants. This would involve training the neural network using samples of known concentrations of the target molecule in order to recognize the spectral fingerprint of that molecule.

[0189] The array could be disposed onto a microneedle surface, with each needle or group of needles representing one pixel. This would facilitate real-time monitoring of biomarkers or drugs within interstitial fluid. The array could be printed onto a wearable sensor in order to monitor changes in the composition of sweat. The array could be printed onto a lateral flow device in order to separate components of the serum, urine, or saliva prior to fluorescence measurement.

[0190] By incorporating this sensor into cell-culture flasks, it is possible to constantly monitor the presence and concentrations of biomolecules, such as metabolites, and to detect contamination such as mycoplasma, bacteria, and fungus. By incorporating the sensor intoshipping packaging or freight containers, it is possible to detect the presence, quality, or purity of molecules such as drugs or explosives (e.g., with applications in border control).[00191 J In addition, the array could be used as an anti -counterfeiting label, due to the difficulty of reproducing a specific array without knowing the exact composition of each pixel. The authenticity of the array could be demonstrated by adding solutions or volatiles of known composition in order to reveal their spectral fingerprints. The composition of the array and of the test solutions or mixture would be predefined information for the entity producing the anticounterfeiting labels.

[0192] A nanotube array used as an anti-counterfeiting label may lack any environmental sensitivity. Each pixel or group of pixels may have a different fluorescence spectrum (due to differences in nanotube ink composition), providing sufficient complexity to prevent forgery. For the purposes of using the nanotube arrays as anti-counterfeiting labels, custom ink may be synthesized by different organizations using additive compounds which affect the fluorescence spectrum of each ink (the composition of which may be specific for that organization), or by filtering a generic ink formulation through a custom separation column (the composition of which may be specific) such that only nanotubes with specific dimensions or surface treatments pass through.

[0193] Arrays can be any size, such as micrometer scale for high throughput imaging using fluorescence microscopy, or millimeter or centimeter scale for analysis using point-of-care devices such as cameras or mobile phones. The arrays may also be a one-dimensional barcode, or another pattern entirely. Arrays can be produced via inkjet printing, micro-pipetting, aerosol printing, screen printing, or other technologies. Inkjet printing may be the most suitable for production of low-cost arrays.

[0194] Pixels can be individually multiplexed, containing multiple different SWCNT sensors. These SWCNT sensors could potentially interact with each other differently in the presence of analyte (e.g., increased or decreased non-radiative energy transfer efficiency). The composition of several pixels can be repeated in the same array to increase reproducibility and accuracy of the analysis.

[0195] The sensor may have each pixel providing a unique or semi-unique response to a particular analyte. In some embodiments, each pixel may be created using a unique SWCNT sensor. In some embodiments, the same SWCNT sensors can be deposited onto multiple spots on a substrate that has varying physical properties at different locations. For example, this could take the form of a polymeric sheet with gradients in pore size and hydrophobicity along each axis. This sheet could be the substrate itself or could be placed over the SWCNT sensors such that the analyte has to pass through the sheet in order to reach the SWCNT sensors.

[0196] Referring now to FIG. 8A, depicted is a block diagram of an example system 800 including SWCNT sensors. In overview, the system 800 may include at least one device 805 with at least one SWCNT sensor 810 (e.g., as disclosed herein), at least one excitation light source 815, and at least one detector 820, among others. The device 805 may house, contain, or otherwise hold the SWCNT sensor 810. In some embodiments, one or both of the excitation source 815 and the detector 820 may be part of the device 805. In some embodiments (e.g., as depicted), the excitation source 815 and the detector 820 may be part of the device 805.

[0197] The device 805, the SWCNT sensor 810, the excitation light source 815, and the detector 820 may be used to conduct fluorescent imaging, spectroscopy, or microscopy in evaluating at least one sample 812. The device 805 may house, contain, or otherwise hold a set of SWCNT sensor 810s. Each SWCNT sensor 810 may have different fluorescence responses to react differently to the sample 812 placed thereon. The excitation light source 815 may radiate, produce, or otherwise emit fluorescent light to illuminate a sample in contact with the SWCNT sensor 810. The SWCNT sensors 810 may be used to identify molecules of interest in the sample (e.g., identifying biomarkers for cancer or pollutants in a liquid sample), confirming the composition of a sample (e.g., a drug composition), validating the authenticity of the sample (e.g., as an anti-counterfeit measure), establish an identity (e.g., source, origin, or manufacturer) of the sample, track a chain of ownership of the sample (e.g., establish provenance), and enforcing security policies, among others. The SWCNT sensors 810 may be situated in a wide variety of applications, such as diagnostic, anti-counterfeiting, validating compositions, quality control, biomarker detection, microfluidic applications, or security applications, among others.The detector 820 may be any device to acquire images of samples illuminated by the excitation light source 815 through the SWCNT sensor 810. The detector 820 may be, for example, a fluorescence microscope, a charge-coupled device (CCD), or a fiber optical device, among others.

[0198] At least one sample 812 may be in contact with the SWCNT sensor 810. The contacting between the sample 812 and the SWCNT sensor 810 may form a mixture. The sample 812 may be any material or object to be analyzed using the SWCNT sensor 810 for molecules of interest. The sample 812 may be of an item, object, or material in any phase, such as liquid, solid, or gas, among others, or any combination thereof. In some embodiments, the sample may include a biological sample, such as skin, saliva, blood, plasma, serum, urine, feces, sweat, breath, tears, serous fluids, subcutaneous fluid, biopsy samples, bacteria, viruses, fungus, drugs, cultured cells, or cell media, among others. The biological sample may be acquired or obtained from a human subject or an animal subject. In some embodiments, the sample 812 may include a non-biological sample (e.g., a drug, a forensic sample, environmental pollutant, explosive, consumer good, product of manufacture, or any other item), among others. For example, the sample 812 may be an item of value, such as an identification document (e.g., passport or driver’s license), currency (e.g., coin or paper notes), a weapon, a bag, a computing device (e.g., tablet, smartphone, laptop, or desktop), or a writing utensil, among others. In some embodiments, the sample 812 may include a food substance (e.g., fruit, vegetables, grains, plants, meats, cooking oil or derivatives therefrom), fuel (e.g., motor oil, gasoline, or diesel), a perfume (e.g., fragrant oils, aroma compounds, fixatives, or solvents, or any combination thereof), a beverage (e.g., wine, beer, liquor, soda, or water), a construction material (e.g., wood, concrete, brick, cement, steel, glass, stone, or masonry), or a storage container (e.g., metallic, polymer, or wood material), among others.

[0199] In some embodiments, the sample 812 may be attached, affixed, or otherwise joined to at least one of side of a SWCNT sensor 810. For example, the sample may be affixed to the one side of the SWCNT sensor 810 using an adhesive. In this example, the SWCNT sensor 810 affixed to the sample may be used as a barcode to determine an identity, validate an authenticity,or track a chain of ownership of the sample, among others. The sample (e.g., cells or cell growth media) may also be placed in contact with one side of the SWCNT sensor 810.[00200J When the sample 812 is biological material, the sample may be obtained from a subject. The subject may be a human or an animal at risk of cancer or suffering from a disease or cancer. The disease may include, for example, a blood disease (e.g., anemia, leukemia, hemophilia, sickle cell disease), diabetes, kidney disease, a liver disease (e.g., hepatitis or cirrhosis), or a thyroid disorder, among others. The cancer may include, for example, a bone cancer (e.g., osteosarcoma, chondrosarcoma, chordoma, or Ewing sarcoma), a lung cancer (e.g., non-small cell lung cancer (NSCLC) or Small cell lung cancer (SCLC)), a breast cancer (e.g., Ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), Lobular carcinoma in situ (LCIS), and Invasive lobular carcinoma (ILC)), or a colon cancer (e.g., adenocarcinoma, Gastrointestinal carcinoid tumors, lymphomas), among others. The cancer may be present in the sample in the form of tumorous cells. The sample 821 may be taken, collected, or otherwise obtained from at least one anatomical site associated with the disease or cancer within the subject. The sample can include tissue, bone, cartilage, or any other portion of the organ from the anatomical site. The anatomical site may be a primary site or a secondary (e.g., metastasized) site for the cancer. For example, when the subject is at risk of or suffering from thyroid cancer (e g., papillary, follicular, medullary, or anaplastic), the clinician examining the subject may collect the samples 812 via biopsy from the thyroid of the subject.

[0201] The device 805 may include a set of SWCNT sensors 810A-N (hereinafter generally referred to as SWCNT sensors 810) disposed, situated, or arranged along the substrate 816. Each of the SWCNT sensors 810 (sometimes herein referred to as pixels) may span or extend at least partially (e.g., as depicted) or fully between sides of the substrate 816. The set of SWCNT sensors 810 may be disposed, arrayed, or otherwise arranged in a one-dimensional line (e.g., a line or a curve along the substrate 816), a two-dimensional (e.g., across a region of a surface of the substrate 816), or a three-dimensional volume (e.g., with some SWCNT sensors 810 deposited on top of one another within the substrate 816). In some embodiments, the set of SWCNT sensors 810 may be disposed, arrayed, or otherwise arranged along the substrate 816 ina pattern. The pattern may be used to establish an identity of the sample 812, validate an authenticity of the sample 812, or track a chain of ownership of the sample 812, among others. For example, the SWCNT sensors 810 in the device 805 may be used as a barcode affixed to a product or item corresponding to the sample 812 to establish the identity, validate the authenticate, or track the chain of ownership of the product or item. In some embodiments, the SWCNT sensors 810 may be grafted to, confined within, adjacent to, or otherwise colocalized with one or more binding agents. The binding agents may include, for example, antibodies, proteins, peptides, nanobodies, antigens, enzymes, aptamers, or molecularly imprinted polymers, among others.

[0202] The set of SWCNT sensors 810 may be arranged in any pattern, such as a linear formation, grid formation, staggered formation, a cross formation, or irregular pattern. Each SWCNT sensor 810 may correspond to a respective portion along the at least one side 814substrate 816. The portion may be of any shape, such as circular, regular, triangular, pentagonal, hexagonal, polygonal, or irregular, among others. The diameter of the SWCNT sensors 810 may be of any dimension ranging between nanometers and millimeters. For example, the diameter of the SWCNT sensors 810 may range between 0.5-3 nm for among others. Each SWCNT sensor 810 may be separated from at least one other SWCNT sensor 810 at a distance. For instance, one SWCNT sensor 810 may have a distance of between 1 nm and 1 cm, relative to the adjacent SWCNT sensor 810.

[0203] Each of the SWCNT sensors 810 may have or be characterized by a unique fluorescence response profile to the fluorescent light. In the device 805, at least one SWCNT sensor 810 may have a fluorescence response profile different from another SWCNT sensor 810. In some embodiments, at least one of the SWCNT sensors 810 may be configured with an environmental sensitivity with respect to fluorescence in at least one of a spatial or temporal domain. The environmental sensitivity may correspond to, may be correlated with, or otherwise may include a change in at least one of an absorbance intensity or a spectral characteristic of the SWCNT sensor 810. For example, when the device 805 is used as a barcode affixed to a product corresponding to the sample 812, each of the SWCNT sensors 810 may have a differentfluorescence response profile. Due to the different response profile or environmental sensitivity (or both), each SWCNT sensor 810 may generate fluorophores with unique fluorescence spectra when affixed to the sample 812.

[0204] Upon placement, disposal, or addition of the sample 812 onto the at least one side 814 of the substrate 816, the SWCNT sensors 810 can undergo a reaction to the sample 812, changing the fluorescent properties of the SWCNT sensors 810. The fluorescence response profile may identify, define, or characterize a change in fluorescence properties of the SWCNT sensor 810 in response to undergoing a reaction (e.g., a physicochemical reaction) with the sample 812. Each SWCNT sensor 810 may absorb the fluorescent light emitted upon the at least one side 814 at a particular wavelength and emit another light signal in accordance with the fluorescence properties of the SWCNT sensor 810. The reaction may be a change in the intensity, color, or pattern of the transmitted light. The sample 812 itself may be used to treat the set of SWCNT sensors 810 to alter, set, or otherwise change the fluorescent properties of the SWCNT sensors 810.

[0205] The reaction of the individual SWCNT sensors 810 with the sample 812 may include, for example, an electrostatic interaction, a hydrophobic interaction, a specific interaction, an oxidation reaction, a reduction reaction, or an ionic reaction, among others. Electrostatic interactions may correspond to the attraction or repulsion between charged particles between the SWCNT sensor 810 and the sample 812. Hydrophobic interactions may correspond to interactions between nonpolar molecules of the SWCNT sensor 810 in the presence of water in the sample 812. Specific interactions refer to certain types of interactions between specific molecules or functional groups in the sample 812 with the SWCNT sensor 810. Oxidation may correspond to a reaction in which SWCNT sensor 810 loses electrons or changes its oxidation state. Reduction may correspond to the gain of electrons by the SWCNT sensor 810. An ionic interaction may correspond to the electrostatic interactions to form positive or negatively charged ions between the SWCNT sensor 810 and the sample 812.

[0206] The fluorescence response profile may, for example, include an excitation wavelength, an emission wavelength, a quantum yield, a Stokes’ shift, or dark fraction, amongothers. The excitation wavelength may define a range of wavelengths of the incoming fluorescent light the materials in the SWCNT sensor 810 can absorb. The emission wavelength may define a range of wavelengths at which the SWCNT sensor 810 can emit the light signals. The quantum yield may identify a ratio of fluorescent light photons that are emitted through fluorescence through the SWCNT sensor 810. The Stokes’ shift may define a difference between the excitation and emission wavelengths. The dark fraction may identify a proportion of molecules active in the SWCNT sensor 810 for fluorescence emission.

[0207] The fluorescence response profile may depend on specific properties of the SWCNT sensor 810 and the molecular interactions occurring within or around the SWCNT sensor 810. In some embodiments, when the SWCNT sensors 810 are carbon nanotubes, the differences in the fluorescence response profile may be due to differences in: structural defects, chirality, polymer coating, surfactant, peptide, protein, saccharide, or other modification to carbon nanotubes, among others. The SWCNT sensors 810 can be structured to be sensitive to a particular molecule. For example, when anti -counterfeit inks or chemical makers are applied to a sample, the fluorescent light can create a specific pattern or color change that is difficult to replicate. The device 805 may be exposed to additional solutions or gases to instigate, initiate, or otherwise initiate a change in the fluorescent profiles of the SWCNT sensor 810. With the change to preidentified fluorescent profiles, the SWCNT sensors 810 on the device 805 may be used for various purposes, including validation. The fluorescence response profile of each of the SWCNT sensors 810 may be dependent on the structure of the SWCNT sensor 810 itself, such as the presence of a coating agent, a defect, a chirality, polymer surfactant, peptide, or saccharide

[0208] The coating agent may correspond to a substance used to modify or encapsulate SWCNT sensor 810 to modify the fluorescence response profile. The defect may correspond to inserted or manufactured abnormalities or imperfections (e.g., impurities, clustering, photobleaching, or inhomogeneity) within the SWCNT sensor 810. The chirality may correspond to an arrangement of molecules in the structure of the SWCNT sensor 810, such as dichroism, asymmetry, or mirroring, among others. The presence of polymers may correspond to inclusion of polymer molecules within the molecules of the SWCNT sensor 810. Thepresence of surfactant (also referred to herein as surface-active agent) may correspond to inclusion of compounds to modify solubility, stability, or dispersion of molecules within the SWCNT sensor 810. The presence of peptide may be to introduce chain of amino acids into the fluorophore molecules in each SWCNT sensor 810.

[0209] The arrangement of the SWCNT sensor 810 along the at least one side 814 of the substrate 816 and the fluorescence response profile of each SWCNT sensor 810 can be set or configured based on an application. For example, for the purposes of anti-counterfeit labeling, the substrate 816 may correspond to a surface of an item (e.g., as a label), and the set of SWCNT sensors 810 may be arranged in a matrix barcode pattern (e.g., a bar code, a quick-response (QR) code, or a universal product code (UPC)) along the surface. The distinct fluorescence patterns can form a QR code or fingerprint. The QR code or fingerprint can be used to identify molecules, specific analytes, patterns, or medical conditions, among others. Each SWCNT sensor 810 may have a different fluorescence response profile, with various additives and structural elements to set the fluorescence properties of the SWCNT sensor 810 in reacting with the molecules of the underlying items. The arrangement and setting of the response profiles may make it difficult for another party to replicate the substrate 816 forming the label, or the item itself. In some embodiments, the arrangement of the plurality of SWCNT sensors 810 in accordance with the pattern may be used to produce a unique fluorescence spectra in response to light.

[0210] The device 805 itself may be assembled, created, or otherwise manufactured in accordance with any number of techniques. For example, the device 805 may be manufactured by printing ink (e.g., carbon nanotube-based ink) to place, deposit, or otherwise arrange onto a material forming the substrate 816. The ink may correspond to the set of SWCNT sensors 810 along the at least one side 814 of the substrate 816. In some embodiments, the ink may initially be generic across the set of SWCNT sensors 810, and then subsequently agents may be added to individually modify the fluorescence response profiles. In some embodiments, the ink may be particular to each respective SWCNT sensor 810, synthesized using additive compounds that affect the fluorescence spectrum of each ink (e.g., allowing for a tailored response profile foreach ink). In some embodiments, the set of SWCNT sensors 810 may be produced, created, or otherwise formed using one or more a fluorophore mixture (e.g., in the form of a solution), particularly an entity. The fluorophore mixture may be modified using at least one an inclusion of additives, a purification of the solution, a size separation, chromatography, or a light treatment, among others. The purification of the solution further comprises separation of carbon nanotubes with different chirality, surface treatment, and length or chemical modification.

[0211] The fluorophore mixture used to form the SWCNT sensors 810 may result in each SWCNT sensor 810 having a unique fluorescence response profile. By configuring the SWCNT sensors 810 in this manner, the set of SWCNT sensors 810 of the device 805 may form a unique bar code to generate fluorophores with unique fluorescence spectra when affixed to the sample 812. As each mixture may vary from one another and may also differ, the SWCNT sensors 810 may be unique to the particular device 805, making it difficult to reproduce the barcode (e.g., as represented by the set of SWCNT sensors 810). The use of different form factors (e.g., two-dimensional or three-dimensional) for the SWCNT sensors 810 may also increase the difficulty of reproducing the barcode corresponding to the set of SWCNT sensors 810.

[0212] In some embodiments, a test solution (sometimes herein referred to as a solution or additive) may be applied, provided, or otherwise administered to the device 805. The test solution may alter, change, or otherwise modify the fluorescence response profile of one or more of the SWCNT sensors 810 of the device 805. In some embodiments, the test solution may be administered to the sample 812 to react with the SWCNT sensors 810 of the device 805. The test solution may include an additive or chemical marker to react with the SWCNT sensors 810 to induce spectral changes. The additive may include, for example, a surfactant (e.g., sodium dodecyl sulfate or sodium cholate), a polymer (e.g., polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and polystyrene sulfonate (PSS)), a functional group (e.g., carboxyl, hydroxyl, or amine), a metal ion (e.g., silver or platinum), a dye (e.g., rhodamine, fluorescein, or cyanine), or biomolecules (e.g., deoxyribonucleic acid (DNA) protein or peptide), among others. In some embodiments, the test solution includes a ligand to bind, conjugate, or otherwise react with the SWCNT sensors 810. The ligand may include, for example, a receptorligand (an agonist or antagonist ligand), an enzyme ligand, a transport protein, an allosteric ligand, or an ionic ligand, among others. The ligand may bind, conjugate, or otherwise react with the recognition agents in the SWCNT sensors 810, such as antibodies, aptamers, and molecularly imprinted polymers, among others.

[0213] The test solution can be administered to the device 805 to induce changes to the fluorescence response profde (e.g., spectral changes), unique to the combination of SWCNT sensors 810 in the device 805 and the composition of the test solution. The spectral changes can serve as a validation technique to verify the authenticity of the device 805. By analyzing the distinct patterns produced by the SWCNT sensors 810, it becomes possible to distinguish genuine sensor arrays (e.g., the device 805) from counterfeits. The pattern created by the interaction between the test solution and the SWCNT sensors 810 may ensure that authorized entities can accurately reproduce or verify the device 805. The addition of the test solution may provide an additional layer of verification that is difficult to replicate without access to the exact formulation.

[0214] In some embodiments, the SWCNT sensors 810 may be conjugated to a recognition agent. The recognition agent may include molecules or compounds to identify or bind to particular targets, be used to induce a particular fluorescence response in the SWCNT sensors 810. In some embodiments, the recognition agents may be used to induce a particular fluorescence response in the SWCNT sensors 810, when administered with the test solution. The recognition agent may include, for example, antibodies, nanobodies, aptamers, DNA, or molecularly imprinted polymers, among others, to selectively bind to target molecules. The conjugation process can include attaching recognition agents to the surface of SWCNT sensors 810. For example, antibodies can target and bind specific proteins or antigens, for use of the device 805 in biomedical diagnostics. Nanobodies may be smaller and more stable than antibodies, but they can provide similar binding capabilities with the added advantage of better tissue penetration and reduced immune response. Aptamers can bind to a wide range of targets with high specificity and affinity, providing a versatile tool for detecting various biomolecules. By incorporating recognition agents, the SWCNT sensor 810 of the device 805 can becomehighly selective and capable of detecting minute concentrations of analytes. In some implementations, the test solution may contain ligands specific for the recognition agent, such as antigens complementary to the antibody, complementary DNA sequences, or the template molecule of the molecularly imprinted polymer. The ligands in the test solution can be selected to interact with their corresponding recognition agents on the device 805, thereby reducing the likelihood of false positives or nonspecific binding

[0215] In some embodiments, the specific recognition agent can be added, included, or otherwise disposed in a defined pattern on the device 805. The placement of the recognition agent can be relative to the SWCNT sensors 810, such as within, atop of, or adjacent to at least one of the SWCNT sensors 810. In some embodiments, multiple recognition agents can be added, included, or otherwise arranged in the SWCNT sensors 810 of the device 805. For example, one recognition agent can be printed on the device 805 in one or more of the SWCNT sensors 810, and be obscured with other non-specific recognition agents. The placement can allow the specific ligands in the test solution to interact with their corresponding recognition agents, leading to distinct spectral changes. When the ligands bind to their specific recognition agents, the resulting fluorescence pattern can reveal the pre-defined arrangement of the specific recognition agents. The pattern of spectral changes can then serve as a unique validation technique, confirming the authenticity of the device 805. By using a mixture of specific and non-specific recognition agents, it can become difficult for unauthorized parties to replicate the precise pattern and spectral response of the device 805, thereby enhancing the security and reliability of the validation process.

[0216] In some embodiments, the scrambled or random DNA sequences (an example of a recognition agent) may be printed on the device 805 relative to the SWCNT sensors 810. For instance, the recognition agent may be printed in a specific pattern (e.g., a brand logo or identifier) atop the SWCNT sensors 810 conjugated to a specific DNA sequence. The use of scrambled or random DNA sequences conjugated to SWCNT sensors 810 and printed across the device 805 can create a uniform to mask the pattern, enhancing the security of the code, makingit challenging for unauthorized entities to discern the exact sequence and pattern of the specific recognition agents.[00217J In some embodiments, the device 805 may be arranged, disposed of, or otherwise situated within a vessel containing the sample 812. For example, the vessel may be an assay, such as a microtiter plate, and the device 805 may be printed within an inside of a microtiter plate well. Each microtiter plate well can contain a unique device 805 pattern with SWCNT sensors 810 conjugated to specific recognition agents, allowing parallel processing of different test solutions 230 and increasing diagnostic efficiency. The fluorescence patterns in each microtiter plate well may be used to identify and validate multiple targets, such as biomolecules, pathogens, or chemical compounds, among others, within the sample 812.

[0218] The excitation light source 815 may radiate, produce, or otherwise emit light to illuminate the sample 812 and the SWCNT sensors 810 in the device 805. The excitation light source 815 may facilitate fluorescent imaging, spectroscopy, or microscopy in evaluating a sample. The light may traverse from the radiating end of the excitation light source 815 through the sample 812 and toward the device 805. The excitation light source 815 may include, for example, a mercury arc lamp, a xenon arc lamp, a light emitting diode (LED), or a laser, among others. The light may have any wavelength, such as wavelengths between 250-750 nm (e.g., fluorescent light). In some embodiments, the light emitted by the excitation light source 815 may be dependent on the fluorophores to be targeted. For example, for blue and green fluorophores, the wavelength may be between 515-525 nm; for green fluorophores, between 500-515 nm; or for red fluorophores, between 550-690 nm, among others.

[0219] In producing, the excitation light source 815 may output the light to illuminate the sample 812 and the SWCNT sensors 810 in the device 805. The light 830 may arrive or reach the at least one side 814 of the device 805. The light 830 may reach the set of SWCNT sensors 810 of the substrate 816 on the at least one side 814. In response, each of the SWCNT sensors 810 may emit, produce, or otherwise transmit light 835. Each SWCNT sensor 810 may absorb the light from the excitation light source 815 and may emit the respective light 835 in accordance with the associated fluorescence response profde. The properties of the respective light signal845, such as the color, intensity, and patterns, may be dependent on the molecules of interest in the sample 812.[00220J The detector 820 may obtain, generate, or otherwise acquire at least one image 840 including a set of light signals 845 A-N (hereinafter generally referred to as a light signal 845) from the device 805. The set of light signals 845 may correspond to the set of SWCNT sensors 810. For example, each light signal 845 may be dependent on the fluorescence response profde of the SWCNT sensor 810 from which the light signal 845 was emitted, and may contain different colors, intensities, or patterns, among others. Each light signal 845 may be, for example, fluorescent light having a wavelength between 250-750 nm. The detector 820 may acquire the image 840 in accordance with fluorescence imaging, microscopy, or spectroscopy, among others. The image 840 may be in the form of an image file (e.g., with a BMP, TIFF, LJPEG, or PNG, among others).

[0221] Referring now to FIG. 8B, depicted is a block diagram of an example system 850 to process light from SWCNT sensors. The system 850 may be part of the system 800. In overview, the system 850 can include at least one image processing system 855. The image processing system 855 may include at least one image parser 860, at least one code generator 865, at least one sample classifier 870, at least one output handler 875, at least one classification model 880, and at least one display 828, among others. Each of the components in the system 850 as detailed herein may be implemented using hardware (e.g., one or more processors coupled with memory), or a combination of hardware and software as detailed herein in conjunction with FIG. 12.

[0222] In further detail, the image processing system 855 may (sometimes herein generally referred to as a computing system or a server) be any computing device comprising one or more processors coupled with memory and software and capable of performing the various processes and tasks described herein. The image processing system 855 may be in communication with the detector, the display 828, and other devices, via a network. The image processing system 855 may be situated, located, or otherwise associated with at least one server group. The server group may correspond to a data center, a branch office, or a site at which one or more serverscorresponding to the image processing system 855 are situated. The image processing system 855 may store, using one or more data structures, an association between the sample and the classification of the molecules of interest of the sample.

[0223] On the image processing system 855, the image parser 860 may retrieve, identify, or receive images of samples via the sensor array 110 from the imaging device 120 to be processed at the image processing system 855. The code generator 865 may generate codes from the images received by the image parser 860. The sample classifier 870 may determine a classification of molecules in the sample using the codes. The output handler 875 may provide information based on the classification of molecules in the sample. The classification model 880 may be any type of machine learning model or artificial intelligence (Al) algorithm to classify molecules or interest in an image. In general, the classification model 880 may have at least one input and at least one output. The output and the input may be related via a set of weights. The input may be at least one image. The output may include the classification of the molecules from the application of the classification model 880 onto the input image in accordance with the set of weights.

[0224] The set of weights of the classification model 880 may define corresponding parameters to be applied to the input image to generate the output image. In some embodiments, the set of weights may be arranged in one or more transform layers. Each layer may specify a combination or a sequence of applications of the parameters to the input and resultant. The layers may be arranged in accordance with the machine learning algorithm or model for the classification model 880. For example, the classification model 880 such as a clustering algorithm (e.g., ^-means clustering), a regression algorithm (e.g., linear or logistic regression), a random forest, a decision tree, a support vector machine (SVM), a Naive Bayesian classifier, or an artificial neural network (e.g., convolutional neural network architecture), among others. The classification model 880 may have been initialized, trained, and established to detect the classification using training data (e.g., in accordance with supervised learning techniques).

[0225] The image parser 860 executing on the image processing system 855 may identify, retrieve, or otherwise receive, via the detector 820, the image 840 of the set of light signals 845.Upon receipt, the image parser 860 may detect or identify the individual set of light signals 845 within the image 840. In some embodiments, the image parser 860 may determine or identify the plurality of light signals 845 of the image 840 as corresponding to the plurality of SWCNT sensors 810 based on a position of each light signal 845 of the plurality of light signals 845 in the image 840 and a position of each of the plurality of SWCNT sensors 810. For example, the image parser 860 may perform image registration to determine the correspondence between each light signal 845 and the corresponding SWCNT sensor 810 based on the positioning. The image registration may be in accordance with any number of techniques, such as intensity-based registration (e.g., mutual information or normalized cross-correlation), feature-based registration (e.g., using object detection, scale-invariant feature transform, or speeded up robust features), or deformable image registration (e.g., using B-spline registration), among others.

[0226] Using the set of light signals 845 in the image 840, the code generator 865 may output, produce, or otherwise generate at least one response code 885. The response code 885 may identify or define a set of responses by the corresponding set of SWCNT sensors 810 of the device 805. The set of responses may be due to the respective fluorescence response profile in each SWCNT sensor 810. The response code 885 may include one or more values for each light signal 845, and may characterize one or more corresponding parameters (e.g., intensity, a color, or pattern) in the respective light signal 845. To generate, the code generator 865 may traverse through the set of light signals 845 identified from the image 840. For each light signal 845 identified from the image 840, the code generator 865 may determine the parameters of the light signal 845. Based on the parameters, the code generator 865 may determine the corresponding code for the response code 885. The determination may be in accordance with a function mapping the parameters to values for creating the response code 885.

[0227] The sample classifier 870 executing on the image processing system 855 may identify or otherwise determine a classification 890 of the molecules of interest of the sample 812 based on the response code 885. The classification 890 may identify the molecules of interest within the sample 812, such as biomarkers for a disease or cancer within the subject, traces for drugs or explosives, and other indications for anti-counterfeit measures, among others. In someembodiments, the classification 890 may identify various characteristics of the disease in the sample 812, such as: a presence or extent of disease, a presence or type of pathogenic organisms, a presence of risk factors or comorbidities, a prediction of prognosis, or other clinically relevant parameters, among others.

[0228] In some embodiments, the classification 890 may identify various characteristics about the material of the sample 812, such as a presence, absence, concentration, quality, or purity of toxic compounds, drugs, explosives, or environmental pollutants, among others. In some embodiments, the classification 890 may identify various biological or chemical properties about the material of the sample 812, such as a pH level, a salt level, a salt type, a redox species, a concentration of a gas (e.g., oxygen), a temperature, a presence of contaminants, or type of cells present, among others. For instance, when a cell or cell growth media is placed in contact with the device 805 as the sample 812, the classification 890 may identify nutrients, metabolites, cell confluency, pH, presence or concentration of toxins, and other biologically relevant parameters, among others.

[0229] In some embodiments, based on the response code 885, the sample classifier 870 may measure, calculate, or otherwise determine a measure indicating concentration (e.g., dosage unit in milligrams, micrograms, or milligrams per milliliter) or purity (e.g., percentage, parts per million (ppm), or parts per billion (ppb)) of a compound in the sample 812 (e.g., an active ingredient for a drug in the sample 812). With the determination, the sample classifier 870 may compare the measure to a threshold. The threshold may indicate a value for the measure at which to identify the drug in the sample 812 as valid (e.g., sufficiently concentrated, high quality, pure, or potent) or invalid (e.g., insufficiently concentrated, low-quality, impure, or nonpotent). For example, the threshold may be used to identify whether there is sufficient concentration and amount of the active ingredient or composition (e.g., organic compound, peptide, protein, agents, mineral compounds, or other pharmacologically active substances) of the drug within the sample 812. If the measure satisfies (e.g., greater than or equal to) the threshold, the sample classifier 870 may generate the classification 890 to indicate the sample812 as valid. Conversely, if the measure does not satisfy (e.g., less than) the threshold, the sample classifier 870 may generate the classification 890 to indicate the sample 812 as invalid.[00230J In some embodiments, the sample classifier 870 may identify or determine a classification 890 to identify a validation of the sample 812 as authenticated or unauthenticated based on the response code 885. The classification 890 may indicate whether the sample 812 is inauthentic (e g., a counterfeit or a forgery) or authentic (e.g., genuine or real). To determine the validation, the sample classifier 870 may compare the determined response code 885 with an expected response code for the sample 812. The expected response code may be identified from a type of object or item for the sample 812. For instance, the user of the image processing system 855 may provide an identification of a product or good. The sample classifier 870 may find or identify the expected response code for the sample 812 to check against the generated response code 885. When the response codes match, the sample classifier 870 may determine or identify the sample 812 as authenticated. Conversely, when the response codes do not match, the sample classifier 870 may determine or identify the sample 812 as unauthenticated.

[0231] In some embodiments, the sample classifier 870 may determine the classification in accordance with a function of the response code 885. The function may include a mapping between values of the response code 885 with a set of candidate classifications. Using the function, the sample classifier 870 may find the candidate classification 890 matching the response code 885 to identify the molecules of interest in the sample 812. With the determination, the sample classifier 870 may store, using one or more data structures, an association between the sample 812 and the classification 890 of the molecules of interest of the sample 812. The data structures may include, for example, an array, a matrix, a linked list, a stack, a queue, a tree, a graph, or a hash table, among others.

[0232] In some embodiments, the sample classifier 870 may apply the classification model 880 to the response code 885 to determine the classification 890. The classification model 880 may have been initialized, trained, and established using a training dataset (e.g., in accordance with supervised learning). The training dataset may identify or include a set of examples. Each example may include a sample response code and a corresponding classification 890 of themolecules of interest. The sample response of the training dataset may be acquired from an instance of the device 805 with the same arrangement of the set of SWCNT sensors 810 with the same fluorescence response profile when reacting to the sample. The sample response in each example may have been applied to the classification model 880 to generate a predicted classification. A loss metric is determined by comparing the predicted classification and the expected classification in the training dataset. Using the loss metric, the classification model 880 may be updated. This process may be repeated until convergence of the classification model 880.

[0233] With the establishment, the sample classifier 870 may input or feed the response code 885 into the classification model 880. In feeding, the sample classifier 870 may process the response code 885 in accordance with the set of weights of the classification model 880. From processing, the sample classifier 870 may produce, output, or otherwise generate the classification identifying the molecules of interest in the sample 812. With the determination, the sample classifier 870 may store, using one or more data structures, an association between the sample 812 and the classification 890 of the molecules of interest of the sample 812.

[0234] The output handler 875 executing on the image processing system 855 may generate or provide an output 895 to identify the classification 890 of the molecules of interest of the sample. In some embodiments, the output handler 875 may format the classification results for presentation or further analysis. The formatting may involve converting the data into a visually accessible format (e.g., charts, graphs, or comprehensive reports). The output 895 can be displayed on a display 828. The display 828 (or a computing device connected thereto) may display, render, or otherwise present the output 895 from the image processing system 855. The output 895 may also include the image 840. In some embodiments, the output handler 875 may provide the output 895 to identify the validation of the sample 812 as one of authenticated or authenticated

[0235] In some embodiments, the system 800 may be used for microfluidic applications. The device 805 may include at least one solid support 825 on which the device 805 is secured, held, or otherwise immobilized. The solid support 825 may be immobilized against a surface orattachment, among others. The solid support 825 may include, for example, a biocompatible gel, a microcapillary, a filter, a mesh, a tubing, or a compartment / dialysis membrane. The device 805 may include a microfluidic chamber containing the at least one SWCNT sensor, wherein the at least one SWCNT sensor is immobilized on a surface or contained in a semi-permeable enclosure. In some embodiments, the device 805 may include a biocompatible gel, a microcapillary, a filter, a mesh, a tubing, a compartment / dialysis membrane, and / or a solid support on or in which the at least one SWCNT sensor is immobilized, among others.

[0236] In some embodiments, the system 800 may be used for single-photon emission applications (e.g., quantum computing or single-photon emission imaging). In response to excitation light 830 emitted by the excitation light source 815, the SWCNT sensor 810 may radiate or emit light 835 in accordance with single-photon emission. The radiation of photons or particles from the SWCNT sensor may be controlled, such that a single photon or particle is transmitted over the given time. The excitation light 830 may be provided to cause the SWCNT sensor 810 to emit single-photons. In some embodiments, the single photon emission by the SWCNT sensor 810 may be in accordance with photon anti -bunching. For example, the SWCNT sensor may emit single photons or particles in a sequential manner, as opposed to a grouped manner. This may be measured by the second-order correlation of the light emitted by the SWCNT being substantially zero (e.g., within 10%). The detector 820 may receive, accept, or otherwise detect the light 835 emitted from the SWCNT sensor 810.

[0237] In some embodiments, the system 800 may be used for quantum computing. The device 805 may include at least one quantum computer. The quantum computer may include one or more components (e.g., integrated circuits, quantum dots, quantum logic gates, and control and measurement planes) to process data using qubits. The quantum computer may use the SWCNT sensor to transmit, radiate, or otherwise emit photons for carrying information (e.g., represented by qubits). The device 805 may be coupled with the excitation light source 815 or the detector 820, or both. In response to excitation light 830 emitted by the excitation light source 815, the SWCNT sensor 810 may radiate or emit light 835 in accordance with singlephoton emission (e.g., carrying qubit or quantum information). The detector 820 may detect thelight 835 emitted by the SWCNT sensor 810. Using the light 835 detected at the detector 820, the quantum computer may perform various quantum computing functions, such as quantum cryptography (e.g., cryptography using quantum superposition or entanglement), quantum key distribution (QKD) (e.g., secure sharing of cryptographic keys using quantum mechanics), quantum communication (e.g., transmission of information using quantum states), or quantum information processing (e.g., processing, manipulation, or computations using qubits), among others.

[0238] In some embodiments, the system 800 may be used for single-photon emission imaging. The device 805 may include an imaging device to perform single-photon emission imaging. The device 805 may be coupled with the excitation light source 815 or the detector 820, or both. In response to excitation light 830 emitted by the excitation light source 815, the SWCNT sensor 810 may radiate or emit light 835 in accordance with single-photon emission. Between the SWCNT sensor 810 and the detector 820, the light 835 may travel or traverse through a scanning volume (e.g., including a sample or object) to be imaged. The detector 820 may detect the light 835 emitted by the SWCNT sensor 810 and passing through the scanning volume. Using the light 835 detected at the detector 820, the imaging device may perform the single-photon emission imaging in accordance with at least one of single-photon emission computed tomography (SPECT) (e.g., to acquire three-dimensional biomedical images of organs), light detection and ranging (LiDAR) (e.g., to map environments), or quantum imaging (e.g., for high-resolution imaging such as microscopy), among others.

[0239] The system 800 may be used for various other applications. In some embodiments, the device 805 can be affixed, placed, or otherwise attached to produce (e.g., fruits, vegetables, or other plants). The SWCNT sensors 810 can be prepared and then applied to the surface of the produce or to containers holding the produce using adhesives or surface treatments that ensure stability and functionality. In some embodiments, the SWCNT sensor 810 can be affixed, placed, or otherwise attached to a container, including the produce, to assess ripeness or detect contamination. The quality and safety of the produce can be monitored using the device 805, as the produce is transported through the supply chain. By scanning the light signals 845 from the-14-SWCNT sensor 810, users can obtain real-time data on the produce ripeness levels and any signs of contamination. The device 805 can be integrated into irrigation systems to monitor soil moisture levels and nutrient content, ensuring optimal growing conditions and preventing over-or under-watering of crops.

[0240] In some embodiments, the device 805 can be used to assess the progress of fermentation in products such as wine, beer, other alcoholic or non-alcoholic beverages, and compost. The SWCNT sensors 810 can be integrated, via coating or embedding the SWCNT sensors 810, into fermentation tanks, barrels, or compost bins. The SWCNT sensor 810 can be applied to fermentation tanks, barrels, or compost bins, where it can interact with the fermenting substrate or the gases released during the fermentation process. This can allow for real-time monitoring of parameters such as pH, temperature, and gas composition that can allow for assessing the progress and quality of fermentation. The SWCNT sensor 810 can provide data on the fermentation status by forming distinct fluorescence patterns that correspond to specific measurements, such as sugar levels, alcohol content, and acidity. The fluorescence (e.g., via the light signals) can be scanned and analyzed to identify the presence and concentration of molecules and analytes involved in the fermentation process. In some embodiments, the SWCNT sensor 810 can be applied to yogurt and cheese production to monitor the levels of lactic acid bacteria, which can ensure consistent product quality.

[0241] In some embodiments, the device 805 may be attached to buildings or construction materials such as concrete and wood to detect signs of decomposition, such as gas release, rot, or mold, which can allow for the early detection of structural issues and environmental hazards, helping to maintain building safety and integrity. The SWCNT sensors 810 can be embedded or coated onto the construction materials during manufacturing or applied to existing structures (e.g., using adhesives or coatings). The device 805 can be used in smart homes to monitor indoor air quality, detecting pollutants like carbon monoxide, volatile organic compounds (VOCs), and mold spores. The SWCNT sensor 810 can be attached to biological implants (e.g., as hip replacements, dental implants, cardiac stents, orthopedic screws, artificial heart valves, pacemakers, etc.), to measure (e.g., using the light signals) biological factors in vivo, allowingfor continuous monitoring of the implant’s environment and detecting potential issues such as infection, inflammation, or implant degradation. The SWCNT sensors 810 can be incorporated into the implant materials during manufacturing or coated onto the implants using biocompatible adhesives.

[0242] In some embodiments, the device 805 can be affixed to the inside of sample tubes used to collect patient blood, urine, or saliva samples, allowing for in-line automated measurement and disease diagnosis at sample collection or handling facilities. The SWCNT sensor 810 can monitor the stability and integrity of the samples during transport and storage, ensuring that they remain viable for accurate testing. Dip-coating or spraying techniques can be used to coat the inner surfaces of the sample tubes with the SWCNT sensors 810. The device 805 can detect (e.g., using the light signals) changes in temperature, pH, and other environmental conditions that might compromise the sample, providing alerts if the sample is at risk of degradation. This can streamline the diagnostic process, providing immediate and accurate data on the sample conditions. The SWCNT sensor 810 can be used in vaccine vials to monitor the stability and potency of the vaccine during transportation and storage to ensure efficacy upon administration. The SWCNT sensor 810 can be affixed to the inside of blood storage containers to measure the quality of blood (e g., following donation, during long-term storage, etc ). For example, this application can ensure that stored blood maintains its viability and safety for transfusions. The SWCNT sensors 810 can be applied to the inner surfaces of blood storage containers (e.g., blood bags, blood collection tubes, plasma bags, platelet storage containers, cryogenic vials, and transfusion sets) using similar coating techniques such as dip-coating, spraying, layer-by-layer assembly, and plasma coating.

[0243] In some embodiments, the device 805 can be affixed to the inside of fish tanks, animal housing, or plant housing to monitor environmental conditions and can allow for continuous observation of factors such as water quality, temperature, and pH levels. The SWCNT sensors 810 can be integrated into the materials of the fish tanks, animal housing, or plant housing during production or by applying them with adhesives or coatings to existing structures. For example, the SWCNT sensor 810 of the device 805 can be used to detect (e.g.,using the light signals) the presence of harmful pathogens or contaminants, providing early warnings to prevent the spread of disease among fish, animals, or plants. The SWCNT sensor 810 can monitor humidity levels and light exposure, ensuring that optimal conditions are maintained for the health and growth of the organisms. The SWCNT sensor 810 can be used to detect (e.g., using the light signals) contamination in a liquid. For example, the light signals from the device 805 placed in a swimming pool can be processed to detect contamination in the water. By integrating the SWCNT sensor 810 with pool monitoring systems, pool managers can receive real-time data on water quality, including levels of contaminants and chemical balance. In some implementations, the SWCNT sensor 810 can be used for monitoring (e.g., using the light signals) wastewater purity at chemical manufacturing sites. By attaching the SWCNT sensor 810 to wastewater outlets, facilities can continuously monitor the water quality, detecting contamination and ensuring compliance with environmental regulations. For wastewater monitoring, the SWCNT sensors 810 can be coated onto the outlet surfaces using techniques that ensure durability and responsiveness to contaminants (e.g., electroplating, sol-gel coating, thermal spraying, and chemical vapor deposition).

[0244] In some embodiments, the device 805 can be attached to the walls or ceiling of chemical manufacturing or handling sites to measure environmental conditions (e g., air quality) and detect contamination and pollution. This application enhances workplace safety by providing real-time data on the presence of harmful substances in the air. The SWCNT sensors 810 can be embedded into the materials of the walls or ceilings during construction or applied as a coating to existing structures. The SWCNT sensor 810 can be used to detect (e.g., using the light signals) disease or specific molecules in urine via attachment to a toilet, urinal, or catheter, allowing for non-invasive and continuous health monitoring, providing valuable data for early disease detection and management. The SWCNT sensors 810 can be applied to the surfaces of these fixtures using biocompatible adhesives or coatings.

[0245] In some embodiments, the device 805 can be integrated into wearable health monitoring devices, such as smartwatches, fitness trackers, and skin patches, to continuously monitor physiological parameters. In some implementations, the SWCNT sensor 810 can detectearly signs of health issues. The wearable health monitoring devices can track parameters such as glucose levels, dehydration, electrolyte balance, and other vital signs. By embedding the SWCNT sensors 810 into the wearable health monitoring devices, users can receive real-time feedback on their health status, and can enable proactive health management and timely interventions. For example, athletes can use the wearable health monitoring devices to monitor hydration levels during intense physical activities. Patients with chronic conditions such as diabetes can benefit from continuous glucose monitoring, reducing the risk of complications and improving overall disease management.

[0246] The SWCNT sensors 810 of the device 805 may be disposed, positioned, affixed, or otherwise situated on the sample 812 for any number of applications. The SWCNT sensor 810 can be printed on or administered to a container to hold the sample 812. The container can include, for example, a cell culture flask, a petri dish, or a roux bottle, among others. The container can be used in laboratory or research setting for the growth of cell cultures, organoids, spheroids, bacteria, or other biological specimens and organisms. The SWCNT sensors 810 can first be synthesized and functionalized as described earlier. The SWCNT sensors 810 can then be printed or coated onto the inner surfaces of the flasks using techniques such as inkjet printing, micro-pipetting, etc. In some implementations, the SWCNT sensors 810 can be utilized in bioreactors to monitor the production of biopharmaceuticals, enabling real-time observation of pH levels, oxygen concentration, and nutrient availability, ensuring optimal growth conditions for the production of vaccines, antibodies, and other therapeutic agents. By incorporating SWCNT sensor 810 into the container, the health, growth, and environmental conditions of the specimens (examples of the sample 812) can be monitored (e.g., using the light signals 845). This application can aid in experimental protocols and can ensure precise control and timely interventions to maintain optimal growth conditions for the biological samples.

[0247] In some embodiments, the device 805 can be integrated into personal protective equipment (PPE) for workers in hazardous environments to continuously monitor exposure to toxic chemicals and provide real-time alerts, enhancing safety protocols. The SWCNT sensor 810 can be used in environmental monitoring systems to detect pollutants and hazardoussubstances in air, soil, and water. By deploying devices 805 in various locations, environmental agencies can monitor the presence of heavy metals, pesticides, industrial chemicals, or other contaminants. For example, the SWCNT sensors 810 can be embedded in buoys for real-time water quality monitoring in lakes and rivers, detecting pollutants (e.g., lead, mercury, nitrates, etc.). In urban settings, the device 805 can be installed in storm drains and sewage systems to monitor and control the discharge of harmful substances into natural water bodies.Example 4: Computing and Network Environment

[0248] Various operations described herein can be implemented on computer systems. FIG.12 shows a simplified block diagram of a representative server system 1200, client computing system 1214, and network 1226 usable to implement certain embodiments of the present disclosure. In various embodiments, server system 1200 or similar systems can implement services or servers described herein or portions thereof. Client computing system 1214 or similar systems can implement clients, described herein. The systems 100 described herein can be similar to the server system 1200. Server system 1200 can have a modular design that incorporates a number of modules 1202 (e.g., blades in a blade server embodiment); while two modules 1202 are shown, any number can be provided. Each module 1202 can include processing unit(s) 1204 and local storage 1206.

[0249] Processing unit(s) 1204 can include a single processor, which can have one or more cores, or multiple processors. In some embodiments, processing unit(s) 1204 can include a general-purpose primary processor as well as one or more special-purpose co-processors, such as graphics processors, digital signal processors, or the like. In some embodiments, some or all processing units 1204 can be implemented using customized circuits, such as application specific integrated circuits (ASICs) or field programmable gate arrays (FPGAs). In some embodiments, such integrated circuits execute instructions that are stored on the circuit itself. In other embodiments, processing unit(s) 1204 can execute instructions stored in local storage 1206. Any type of processors in any combination can be included in processing unit(s) 1204.

[0250] Local storage 1206 can include volatile storage media (e.g., DRAM, SRAM, SDRAM, or the like) or non-volatile storage media (e.g., magnetic or optical disk, flash memory,or the like). Storage media incorporated in local storage 1206 can be fixed, removable, or upgradeable as desired. Local storage 1206 can be physically or logically divided into various subunits, such as a system memory, a read-only memory (ROM), and a permanent storage device. The system memory can be a read-and-write memory device or a volatile read-and-write memory, such as dynamic random-access memory. The system memory can store some or all of the instructions and data that processing unit(s) 1204 need at runtime. The ROM can store static data and instructions that are needed by processing unit(s) 1204. The permanent storage device can be a non-volatile read-and-write memory device that can store instructions and data even when module 1202 is powered down. The term “storage medium” as used herein includes any medium in which data can be stored indefinitely (subject to overwriting, electrical disturbance, power loss, or the like) and does not include carrier waves and transitory electronic signals propagating wirelessly or over wired connections.

[0251] In some embodiments, local storage 1206 can store one or more software programs to be executed by processing unit(s) 1204, such as an operating system or programs implementing various server functions such as functions of the system 100 or any other system described herein, or any other server(s) associated with system 100 or any other system described herein.

[0252] “Software” refers generally to sequences of instructions that, when executed by processing unit(s) 1204, cause server system 1200 (or portions thereof) to perform various operations, thus defining one or more specific machine embodiments that execute and perform the operations of the software programs. The instructions can be stored as firmware residing in read-only memory or program code stored in non-volatile storage media that can be read into volatile working memory for execution by processing unit(s) 1204. Software can be implemented as a single program or a collection of separate programs or program modules that interact as desired. From local storage 1206 (or non-local storage described below), processing unit(s) 1204 can retrieve program instructions to execute and data to process in order to execute various operations described above.

[0253] In some server systems 1200, multiple modules 1202 can be interconnected via a bus or other interconnect 1208, forming a local area network that supports communication betweenmodules 1202 and other components of server system 1200. Interconnect 1208 can be implemented using various technologies including server racks, hubs, routers, etc.[00254J A wide area network (WAN) interface 1210 can provide data communication capability between the local area network (interconnect 1208) and the network 1226, such as the Internet. Technologies can be used, including wired (e.g., Ethernet, IEEE 802.3 standards) or wireless technologies (e.g., Wi-Fi, IEEE 802.11 standards).

[0255] In some embodiments, local storage 1206 is intended to provide working memory for processing unit(s) 1204, providing fast access to programs or data to be processed while reducing traffic on interconnect 1208. Storage for larger quantities of data can be provided on the local area network by one or more mass storage subsystems 1212 that can be connected to interconnect 1208. Mass storage subsystem 1212 can be based on magnetic, optical, semiconductor, or other data storage media. Direct attached storage, storage area networks, network-attached storage, and the like can be used. Any data stores or other collections of data described herein as being produced, consumed, or maintained by a service or server can be stored in mass storage subsystem 1212. In some embodiments, additional data storage resources may be accessible via WAN interface 1210 (potentially with increased latency).

[0256] Server system 1200 can operate in response to requests received via WAN interface 1210. For example, one of the modules 1202 can implement a supervisory function and assign discrete tasks to other modules 1202 in response to received requests. Work allocation techniques can be used. As requests are processed, results can be returned to the requester via WAN interface 1210. Such operation can generally be automated. Further, in some embodiments, WAN interface 1210 can connect multiple server systems 1200 to each other, providing scalable systems capable of managing high volumes of activity. Other techniques for managing server systems and server farms (collections of server systems that cooperate) can be used, including dynamic resource allocation and reallocation.

[0257] Server system 1200 can interact with various user-owned or user-operated devices via a wide-area network such as the Internet. An example of a user-operated device is shown in FIG. 12 as client computing system 1214. Client computing system 1214 can be implemented,for example, as a consumer device such as a smartphone, other mobile phone, tablet computer, wearable computing device (e.g., smart watch, eyeglasses), desktop computer, laptop computer, and so on.

[0258] For example, client computing system 1214 can communicate via WAN interface 1210. Client computing system 1214 can include computer components such as processing unit(s) 1216, storage device 1218, network interface 1220, user input device 1222, and user output device 1237. Client computing system 1214 can be a computing device implemented in a variety of form factors, such as a desktop computer, laptop computer, tablet computer, smartphone, other mobile computing device, wearable computing device, or the like.

[0259] Processing unit(s) 1216 and storage device 1218 can be similar to processing unit(s) 1204 and local storage 1206 described above. Suitable devices can be selected based on the demands to be placed on client computing system 1214; for example, client computing system 1214 can be implemented as a “thin” client with limited processing capability or as a high-powered computing device. Client computing system 1214 can be provisioned with program code executable by processing unit(s) 1216 to enable various interactions with server system 1200.

[0260] Network interface 1220 can provide a connection to the network 1226, such as a wide area network (e.g., the Internet) to which WAN interface 1210 of server system 1200 is also connected. In various embodiments, network interface 1220 can include a wired interface (e.g., Ethernet) or a wireless interface implementing various RF data communication standards, such as Wi-Fi, Bluetooth, or cellular data network standards (e.g., 3G, 4G, LTE, 5G, 6G, etc.).

[0261] User input device 1222 can include any device (or devices) via which a user can provide signals to client computing system 1214; client computing system 1214 can interpret the signals as indicative of particular user requests or information. In various embodiments, user input device 1222 can include any or all of a keyboard, touch pad, touch screen, mouse or other pointing device, scroll wheel, click wheel, dial, button, switch, keypad, microphone, and so on.

[0262] User output device 1237 can include any device via which client computing system 1214 can provide information to a user. For example, user output device 1237 can includedisplay-to-display images generated by or delivered to client computing system 1214. The display can incorporate various image generation technologies, e.g., a liquid crystal display (LCD), light-emitting diode (LED), including organic light-emitting diodes (OLED), projection system, cathode ray tube (CRT), or the like, together with supporting electronics (e.g., digital-to-analog or analog-to-digital converters, signal processors, or the like). Some embodiments can include a device such as a touchscreen that functions as both input and output device. In some embodiments, other user output devices 1237 can be provided in addition to or instead of a display. Examples include indicator lights, speakers, tactile “display” devices, printers, and so on.

[0263] Some embodiments include electronic components, such as microprocessors, storage, and memory that store computer program instructions in a computer readable storage medium. Many of the features described in this specification can be implemented as processes that are specified as a set of program instructions encoded on a computer readable storage medium. When these program instructions are executed by one or more processing units, they cause the processing unit(s) to perform various operations indicated in the program instructions. Examples of program instructions or computer code include machine code, such as is produced by a compiler, and files including higher-level code that are executed by a computer, an electronic component, or a microprocessor using an interpreter. Through suitable programming, processing unit(s) 1204 and 1216 can provide various functionality for server system 1200 and client computing system 1214, including any of the functionality described herein as being performed by a server or client, or other functionality.

[0264] It will be appreciated that server system 1200 and client computing system 1214 are illustrative and that variations and modifications are possible. Computer systems used in connection with embodiments of the present disclosure can have other capabilities not specifically described here. Further, while server system 1200 and client computing system 1214 are described with reference to particular blocks, it is to be understood that these blocks are defined for convenience of description and are not intended to imply a particular physical arrangement of component parts. For instance, different blocks can be but need not be located inthe same facility, in the same server rack, or on the same motherboard. Further, the blocks need not correspond to physically distinct components. Blocks can be configured to perform various operations, e.g., by programming a processor or providing appropriate control circuitry, and various blocks might or might not be reconfigurable depending on how the initial configuration is obtained. Embodiments of the present disclosure can be realized in a variety of apparatus including electronic devices implemented using any combination of circuitry and software.

[0265] While the disclosure has been described with respect to specific embodiments, one skilled in the art will recognize that numerous modifications are possible. Embodiments of the disclosure can be realized using a variety of computer systems and communication technologies, including, but not limited to, specific examples described herein. Embodiments of the present disclosure can be realized using any combination of dedicated components, programmable processors, or other programmable devices. The various processes described herein can be implemented on the same processor or different processors in any combination. Where components are described as being configured to perform certain operations, such configuration can be accomplished, e.g., by designing electronic circuits to perform the operation, by programming programmable electronic circuits (such as microprocessors) to perform the operation, or any combination thereof. Further, while the embodiments described above may refer to specific hardware and software components, those skilled in the art will appreciate that different combinations of hardware or software components may also be used and that particular operations described as being implemented in hardware might also be implemented in software or vice versa.

[0266] Computer programs incorporating various features of the present disclosure may be encoded and stored on various computer readable storage media; suitable media includes magnetic disk or tape, optical storage media such as compact disk (CD) or digital versatile disk (DVD), flash memory, and other non-transitory media. Computer readable media encoded with the program code may be packaged with a compatible electronic device, or the program code may be provided separately from electronic devices (e.g., via Internet download or as a separately packaged computer-readable storage medium).

[0267] Thus, although the disclosure has been described with respect to specific embodiments, it will be appreciated that the disclosure is intended to cover all modifications and equivalents within the scope of the following claims.EQUIVALENTS

[0268] The present technology is not to be limited in terms of the particular embodiments described in this application, which are intended as single illustrations of individual aspects of the present technology. Many modifications and variations of this present technology can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the present technology, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the present technology. It is to be understood that this present technology is not limited to particular methods, reagents, compounds compositions or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0269] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0270] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like, include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, forexample, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.

[0271] All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.

Claims

CLAIMS1. A functionalized single-walled carbon nanotube (SWCNT) that (a) is covalently functionalized with a plurality of molecules and (b) exhibits luminescent sp3defects, wherein the functionalized SWCNT is para-functionalized and / or ortho-functionalized, wherein the plurality of molecules that are covalently functionalized comprise one or more functional groups selected from among a boronic acid group, a carboxyl group, a hydroxyl group, an ester group, an amino group, an amide group, an aldehyde group, a ketone group, an ether group, an acrylate group, an acrylamide group, and a styrene group, and wherein the plurality of molecules that are covalently functionalized are derived from and / or comprise one or more of alcohols, amines, amides, aldehydes, ketones, amino acids, carboxylic acids, acrylate monomers, acrylamide monomers, substituted alkyls, unsubstituted alkyls, aromatics, heteroaromatics, substituted aryls, unsubstituted aryls, sugars, styrene monomers, or target molecules.

2. The functionalized SWCNT of claim 1, wherein the functionalized SWCNT is not encapsulated with a polymer or a surfactant.

3. The functionalized SWCNT of claim 1, wherein the functionalized SWCNT is encapsulated with a polymer or a surfactant, and wherein the plurality of molecules is not conjugated to the polymer or the surfactant.

4. The functionalized SWCNT of claim 3, wherein the polymer is a single stranded DNA (ssDNA), a LNA, a PNA, a peptide, a protein, polyfluorene, polycarbazole, an aryleneethynylene polymer, a polyethylene glycol (PEG) derivative, or a dextran-based polymer.

5. The functionalized SWCNT of claim 3, wherein the surfactant is Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SUS), Sodium n- tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS),sodium n-octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC).

6. The functionalized SWCNT of any one of claims 1-5, wherein the plurality of molecules comprise a nucleic acid, a peptide, or a protein.

7. The functionalized SWCNT of any one of claims 1-6, wherein the functionalized SWCNT exhibits a detectable change in intrinsic fluorescence relative to a native SWCNT’s En emission peak.

8. The functionalized SWCNT of any one of claims 1-7, wherein the functionalized SWCNT is a (6,5) SWCNT, a (7, 3) SWCNT, a (7, 5) SWCNT, or a (8, 4) SWCNT.

9. The functionalized SWCNT of any one of claims 3-8, wherein the polymer is conjugated to the functionalized SWCNT directly or via a linker.

10. The functionalized SWCNT of claim 9, wherein the linker comprises a 6 carbon (C6) linker, polyethylene glycol (PEG), a hydrocarbon, a synthetic polymer, or a biopolymer.

11. The functionalized SWCNT of any one of claims 1-10, wherein the alcohols are primary alcohols, secondary alcohols, or tertiary alcohols.

12. The functionalized SWCNT of any one of claims 1-11, wherein the alcohols are selected from among 1, 2, 4-butanetriol, 1, 2-propanediol, 1, 3 -propanediol, 1, 4-butanediol, 1- butanol, 1 -hexanol, 1 -pentanol, 1 -propanol, 2-methyl-l -propanol, 2-propanol, ethanol, methanol, phenol, and tert-butanol.

13. The functionalized SWCNT of any one of claims 1-10, wherein the amines are primary amines, secondary amines, tertiary amines, aliphatic amines, or aromatic amines.

14. The functionalized SWCNT of any one of claims 1-10 or 13, wherein the amines are selected from among 1, 2-diaminoethane or tert-butyl amine.

15. The functionalized SWCNT of any one of claims 1-10, wherein the amino acids are naturally occurring amino acids, unnatural amino acids, L-amino acids, or D-amino acids.

16. The functionalized SWCNT of any one of claims 1-10 or 15, wherein the amino acids are selected from among alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

17. The functionalized SWCNT of any one of claims 1-10, wherein the carboxylic acids are primary carboxylic acids, secondary carboxylic acids, tertiary carboxylic acids, aliphatic carboxylic acids, or aromatic carboxylic acids.

18. The functionalized SWCNT of any one of claims 1-10 or 17, wherein the carboxylic acids are selected from among acetic acid, propionic acid, crotonic acid, and pivalic acid.

19. The functionalized SWCNT of any one of claims 1-10, wherein the acrylamide monomers are selected from among acrylamide, N, N-methylenebisacrylamide, 2- acrylamido-2-m ethylpropane sulfonic acid, 3-(acrylamido)phenylboronic acid, N- isopropyl acrylamide, and n-tert-butylacrylamide.

20. The functionalized SWCNT of any one of claims 1-10, wherein the acrylate monomers are selected from among acrylic acid, methylacrylic acid, methacrylic acid, acryloxyethyl thiocarbamoyl rhodamine, 2, 2, 2, -trifluoroethyl methacrylate, and bis[2- (methacry 1 oy 1 oxy )ethy 1 ] phosphate.

21. The functionalized SWCNT of any one of the preceding claims, wherein the target molecule is selected from among sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, sodium deoxy cholate, poly(N -isopropylacrylamide), mal eimide, biotin, adenine, cytosine, guanine, thymine, uracil, dimethyl sulfoxide, lipoic acid, methanesulfonic acid, and ethanesulfonic acid.

22. A SWCNT sensor comprising at least one functionalized SWCNT of any one of claims 1- 21.

23. A device comprising at least one SWCNT sensor of claim 22 and a solid support on which the device is immobilized.

24. The device of claim 23, wherein the solid support comprises a biocompatible gel, a microcapillary, a filter, a mesh, a tubing, or a compartment / dialysis membrane.

25. The device of any one of claims 23-24, wherein the device comprises a microfluidic chamber containing the at least one SWCNT sensor, wherein the at least one SWCNT sensor is immobilized on a surface or contained in a semi-permeable enclosure.

26. A system comprising: the device of any one of claims 23-25, an excitation light source;and a detector for detecting light emitted from the at least one SWCNT sensor in the device following excitation by the excitation light source.

27. The system of claim 26, wherein the device comprises a biocompatible gel, a microcapillary, a filter, a mesh, a tubing, a compartment / dialysis membrane, and / or a solid support on or in which the at least one SWCNT sensor is immobilized.

28. The system of claim 26 or 27, wherein the excitation light source emits near-infrared light or light having a wavelength greater than 700 nm.

29. The system of any one of claims 26-28, wherein the detector detects fluorescent light.

30. The system of any one of claims 26-29, wherein the device is shaped and sized for subcutaneous, intraperitoneal, intrauterine, or intravenous implantation.

31. The system of any one of claims 26-29, wherein the device is shaped and sized for delivery via injection.

32. The system of any one of claims 26-29, wherein the device is configured for attachment to or embedding within a wall of a body cavity, lumen, or organ.

33. The system of claim 32, wherein the body cavity, lumen, or organ comprises a member selected from the group consisting of uterine cavity, cranial cavity, vertebral canal, thoracic cavity, abdominal cavity, pelvic cavity, artery, vein, gastrointestinal tract, bronchi, renal tubules, urinary collecting ducts, vagina, uterus, fallopian tubes, adrenal gland, bone, esophagus, heart, larynx, mouth, pituitary gland, muscle, spleen, thyroid, anus, brain, eye, hypothalamus, liver, nose, prostate, skin, stomach, ureter, appendix, gallbladder, kidney, lung, pancreas, rectum, small intestine, thymus, urethra, bladder, ear, genitals, large intestine, lymph node, parathyroid gland, salivary gland, spinal cord, and trachea.

34. The system of any one of claims 26-33, wherein the detector and the excitation light source are part of a unit.

35. The system of claim 34, wherein the unit comprises a handheld unit positioned outside the subject or within a body cavity of the subject.

36. The system of claim 26, wherein the at least one SWCNT sensor is configured to emit the light in accordance with single-photon emission.

37. The system of claim 36, wherein the device further comprises a quantum computer coupled with the detector to detect the light from the SWCNT sensor.

38. The system of claim 37, wherein the quantum computer is configured to use the light detected at the detector to perform at least one of quantum cryptography, quantum key distribution (QKD), quantum communication, or quantum information processing.

39. The system of any one of claims 36, wherein the device comprises an imaging device coupled with the detector and configured to perform single-photon emission imaging.

40. The system of any one of claims 36-38, wherein the imaging device is configured to use the light detected at the detector to perform the single-photon emission imaging in accordance with at least one of single-photon emission computed tomography (SPECT), light detection and ranging (LiDAR), or quantum imaging.

41. A kit comprising the SWCNT sensor of claim 22, at least one container and instructions for use.

42. The kit of claim 41, wherein the at least one container is an ampule, a vial, a cartridge, a reservoir, a lyo-ject, or a pre- filled syringe.

43. A method for preparing functionalized SWCNTs comprising:incubating a plurality of native SWCNTs with a plurality of molecules in the presence of a Fenton-like metal and hydrogen peroxide under conditions that permit covalent attachment of the plurality of molecules to the native SWCNTs, wherein the plurality of molecules are selected from among alcohols, amines, amides, aldehydes, ketones, amino acids, carboxylic acids, alkyls, aromatics, heteroaromatics, aryls, acrylate monomers, acrylamide monomers, sugars, styrene monomers, and target molecules.

44. The method of claim 43, wherein the Fenton-like metal is Fe, Mn, Ce, Cu, Ag, or Mn.

45. The method of claim 43 or 44, wherein the Fenton-like metal is present in a concentration that ranges from 10 nM to 35 pM.

46. The method of any one of claims 43-45, wherein the plurality of native SWCNTs are incubated with the plurality of molecules for about 5 minutes to about 12 hours.

47. The method of any one of claims 44-46, wherein the Fenton-like metal is derived from FeBr, Feh, ferrocene, ferrocene-derivatives (e.g. ferrocene carboxylic acid), iron(II) trifluoromethane sulfonic acid, FeCLs, or Fe(III) tosylate.

48. The method of any one of claims 43-47, further comprising encapsulating the plurality of native SWCNTs with a polymer or a surfactant, wherein the plurality of molecules are not conjugated to the polymer or the surfactant.

49. The method of claim 48, wherein the polymer is a single stranded DNA (ssDNA), a LNA, a PNA, a peptide, a protein, polyfluorene, polycarbazole, an aryleneethynylene polymer, a polyethylene glycol (PEG) derivative, or a dextran-based polymer.

50. The method of claim 48, wherein the surfactant is Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SUS), Sodium n-tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n- octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC).

51. The method of any one of claims 43-50, wherein the plurality of native SWCNTs are incubated with the plurality of molecules in the presence of UV or light irradiation.

52. An imaging method comprisinga. contacting the SWCNT sensor of claim 22 with a chemical or a biological sample to form a mixture;b. exposing the mixture to excitation light; andc. detecting light emitted by the at least one SWCNT sensor in the mixture following excitation by the excitation light.

53. An imaging method comprisinga. administering the SWCNT sensor of claim 22 to a subject;b. exposing the subject to excitation light; andc. detecting light emitted by the at least one SWCNT sensor in the subject following excitation by the excitation light.

54. The method of claim 52 or 53, wherein the detecting comprises obtaining images of cells or tissue of the biological sample or the subject.

55. A method for detecting an analyte in a biological sample comprisinga. contacting the SWCNT sensor of claim 22 with a biological sample to form a mixture;b. exposing the mixture to excitation light; andc. detecting a wavelength shift in emission electromagnetic radiation (EMR) and / or an intensity shift and / or another change in the spectral characteristics of emission EMR, whereupon reaction of the analyte with the plurality of molecules present on the functionalized SWCNT results in a detectable change in the emission EMR, thereby identifying the presence of the analyte.

56. A method of performing single-photon emissions, comprising:a. providing the SWCNT sensor of claim 22;b. exposing the SWCNT sensor to excitation light; andc. detecting light emitted by the at least one SWCNT sensor in accordance with single-photon emissions.

57. The method of claim 56, further comprising performing a quantum computing function using the light emitted by the at least one SWCNT sensor.

58. The method of claim 57, wherein the quantum computing function comprises at least one of quantum cryptography, quantum key distribution (QKD), quantum communication, or quantum information processing.

59. The method of claim 56, further comprising performing single-photon emission imaging using the light emitted by the at least one SWCNT sensor.

60. The method of claim 59, wherein the single-photon emission imaging comprises at least one of single-photon emission computed tomography (SPECT), light detection and ranging (LiDAR), or quantum imaging.

61. A method of classifying molecules of interest, comprising:contacting a sample having molecules of interest with a plurality of SWCNT sensors of claim 22, each of the plurality of SWCNT sensors having a respective fluorescence response profile in reacting to the sample;emitting fluorescent light toward the plurality of SWCNT sensors to illuminate a sample having molecules of interest;acquiring, by an imaging device, an image of a plurality of light signals corresponding to the plurality of SWCNT sensors;receiving, by a computing system, via the imaging device, the image of the plurality of light signals from the plurality of SWCNT sensors;generating, by the computing system, using the plurality of light signals of the image, a response code defining a plurality of responses by the corresponding plurality ofSWCNT sensors to the fluorescent light due to the respective fluorescence response profile in each SWCNT sensor of the plurality of SWCNT sensors;determining, by the computing system, a classification of the molecules of interest of the sample based on the response code; andproviding, by the computing system, an output to identify the classification of the molecules of interest of the sample.

62. The method of claim 61, wherein the classification identifies at least one of: presence or extent of disease, presence or type of pathogenic organisms, presence of risk factors or comorbidities, prediction of prognosis, or clinically relevant parameters.

63. The method of claim 61, wherein the classification identifies at least one of: presence, concentration, quality, or purity of toxic compounds, drugs, or environmental pollutants.

64. The method of claim 61, wherein the classification identifies at least one of: pH level, salt level or salt type, redox species, concentration of oxygen or other gas, temperature, presence of contaminants, or type of cells present.

65. The method of claim 61, wherein the sample comprises at least one of a cell or a cell growth medium, and wherein the classification identifies at least one of: a presence or concentration of nutrients, presence or concentration of metabolites, cell confluency; pH, presence, or concentration of toxins, or a biological parameter.

66. A method of validating authenticity of samples, comprising:emitting, by a light source, fluorescent light to illuminate a sample in contact with a plurality of SWCNT sensors of claim 22 arranged in accordance with a pattern, each of the plurality of SWCNT sensors having a respective fluorescence response profile in reacting to the sample;acquiring, by an imaging device, an image of a plurality of light signals corresponding to the plurality of SWCNT sensors, the plurality of light signals capturing the pattern on the sample;receiving, by a computing system, via the imaging device, the image of the plurality of light signals from the plurality of SWCNT sensors;generating, by the computing system, using the plurality of light signals of the image, a response code corresponding to the pattern, the response code defining a plurality of responses by the corresponding plurality of SWCNT sensors to the fluorescent light due to the respective fluorescence response profile in each SWCNT sensor of the plurality of SWCNT sensors;determining, by the computing system, a validation of the sample as one of authenticated or unauthenticated based on the response code; andproviding, by the computing system, an output to identify the validation of the sample as one of authenticated or unauthenticated.

67. The method of claim 66, wherein the pattern is configured to at least one of: (i) establish an identity, (ii) validate an authenticity, or (iii) track a chain of ownership of the sample 68. A method for preparing functionalized SWCNTs comprising:incubating a plurality of native SWCNTs with a plurality of molecules in the presence of heat and hydrogen peroxide under conditions that permit covalent attachment of the plurality of molecules to the native SWCNTs, wherein the plurality of molecules are selected from among alcohols, amines, amides, aldehydes, ketones, amino acids, carboxylic acids, alkyls, aromatics, heteroaromatics, aryls, acrylate monomers, acrylamide monomers, sugars, styrene monomers, and target molecules.

69. The method of claim 68, wherein the plurality of native SWCNTs are incubated with the plurality of molecules for about 5 minutes to about 35 minutes.

70. The method of any one of claims 68-69, further comprising encapsulating the plurality of native SWCNTs with a polymer or a surfactant, wherein the plurality of molecules are not conjugated to the polymer or the surfactant.

71. The method of claim 70, wherein the polymer is a single stranded DNA (ssDNA), a LNA, a PNA, a peptide, a protein, polyfluorene, polycarbazole, an aryleneethynylene polymer, a polyethylene glycol (PEG) derivative, or a dextran-based polymer.

72. The method of claim 71, wherein the surfactant is Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), Sodium n-undecyl sulfate (SUS), Sodium n-tridecyl sulfate (StS), sodium n-decyl sulfate (SdS), sodium n-nonyl sulfate (SNS), sodium n- octyl sulfate (SOS), sodium deoxycholate (DOC), sodium dodecylbenzenesulfonate (SDBS), or sodium cholate (SC).

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