TECHNICAL FIELD

Systems and methods related to a polymer-nanostructure composition for selective molecular recognition are generally described.

BACKGROUND

Molecular recognition and signal transduction are two of the main challenges in sensor design. Molecular recognition can occur when a folded and constrained heteropolymer, orientated in three dimensional space creates a binding pocket or surface that can be identified by a specific counter-part. Nature generally offers few ways to enable molecular recognition, including antibodies and aptamers. Scientists and engineers can borrow from nature to gain analyte specificity and sensitivity, using natural antibodies as vital components of the sensor. However, antibodies can be expensive, fragile, and unstable, easily losing biological activity upon modification, such as immobilization, and exhibit batch-dependent variation. These characteristics can limit their use in widespread applications. Moreover, certain molecules of interest do not have a naturally existing antibody, including toxins, drugs and explosives.

Even with a solution for molecular recognition, measuring the analyte binding event can remain a challenge. For fluorescence-based sensors, a common method has been through Förster resonance energy transfer (FRET) between acceptor and donor fluorophores; however, such sensors usually require labeling. In certain circumstances, fluorescence based sensors can utilize fluorophores that photobleach over time, significantly limiting their capability for long-term continuous monitoring. Consequently, improved systems and methods for molecular recognition and detection are needed.

SUMMARY

In one aspect, a composition can include a complex, where the complex can include a nanostructure and a polymer, the polymer adsorbed on the nanostructure and the polymer being free from selective binding to an analyte in the absence of being adsorbed on the nanostructure, and a selective binding site associated with the complex.

In another aspect, a method for analyzing a sample for an analyte can include providing a composition which can include a complex, where the complex can include a nanostructure and a polymer, the polymer adsorbed on the nanostructure and the polymer being free from selective binding to an analyte in the absence of being adsorbed on the nanostructure, and a selective binding site associated with the complex, exposing the composition to a sample, monitoring a property of the composition, and determining a presence of an analyte in the sample based on the property.

In another aspect, a system can include a composition which can include a complex, where the complex can include a nanostructure and a polymer, the polymer adsorbed on the nanostructure and the polymer being free from selective binding to an analyte in the absence of being adsorbed on the nanostructure, and a selective binding site associated with the complex, an electromagnetic radiation source having an excitation wavelength directed at the composition, and a detector configured to receive an emission wavelength from the composition.

In some embodiments, the nanostructure can be a photoluminescent nanostructure.

In some embodiments, the nanostructure can be a quantum dot, a nanowire, a nanotube, a carbon nanotube or a single-walled carbon nanotube.

In some embodiments, the polymer can be a polysaccharide. The polysaccharide can include peptidoglycans, lipopolysaccharides, amylase, chitin, chitosan, glycogen, cellulose, dextran, functionalized dextran, phenoxy functionalized dextran or boronic acid functionalized phenoxy dextran.

In some embodiments, the polymer can be a polynucleotide. The polynucleotide can be DNA or RNA. The polynucleotide can be single stranded or double stranded. The polynucleotide can be single stranded in one section and double stranded in another section. RNA can include mRNA, siRNA or shRNA.

The polynucleotide can form a structure. Exemplary nucleic acid structures can include an A-form double helix, a B-form double helix, a Z-form double helix, a hairpin, a loop or a stem loop.

The polynucleotide can have less than 100,000, less than 50,000, less than 25,000, less than 10,000, less than 5,000, less than 1,000, less than 500, less than 250, less than 100, less than 75, less than 50, less than 30, less than 25, less than 20, 15, 12, 10, 8, 6 or 4 nucleotides.

The polynucleotide can have a random sequence. The polynucleotide can have an ordered sequence. The ordered sequence can be a predetermined sequence. The ordered sequence can be a repeating sequence. The repeat sequence can include less than 500, less than 400, less than 300, less than 200, less than 100, less than 50, less than 30, less than 25, less than 20, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3 or 2 nucleotides. The polynucleotide can be poly(AT), poly(GT), poly(CT), poly(AG), poly(CG), or poly(AC). The polynucleotide can have a content. The content can be a percentage of a unique nucleotide present in the sequence.

In some embodiments, the polymer can be a polypeptide. In some embodiments, the number of amino acids including the polypeptide can fall within a specific range. For example, the polypeptide can include between 5 and about 50 amino acid residues, or between 5 and about 30 amino acid residues. In other embodiments, the polypeptide can fall within a specific molar mass range. For example, the polypeptide can have a molecular weight of between 400 g/mol and about 10,000 g/mol, or between 400 g/mol and about 6,000 g/mol. The polypeptide can be a protein, having greater than about 50 amino acid residues. The polypeptide can be a fragment of a protein. In some embodiments, the polypeptide can be expressed in a disease state. In other embodiments, the polypeptide can be modified. In some circumstances, the polypeptide can be modified by attaching functional groups. In other circumstances, the polypeptide can be ubiquinated, biotinylated, glycosylated, PEGylated or SUMOylated. The polypeptide can be a biomarker, an enzyme, a receptor, a ligand, a peptide hormone, a neuropeptide, a vasoactive intestinal peptide, a chaperone or an antibody.

In some embodiments, the polypeptide can, in some instances, include a peptide sequence observed in the venom of an animal or a derivative thereof. In some embodiments, the polypeptide can be a member the Mastoparan or Bombolitin families of polypeptides, or derivatives of those polypeptides. The polypeptide can include a mastoparan, mastoparan 7 or mastoparan X.

In some embodiments, the polymer can be a conjugate including a dye moiety. The dye moiety can be located at a terminus of a polymer. The dye moiety can include, for example, a fluorescent dye such as perylene derivatives, anthracene derivatives, indigoid and thioindigoid derivatives, imidazole derivatives, naphthalimide derivatives, xanthene derivatives, thioxanthene derivatives, coumarin derivatives, rhodamine derivatives, thiophene derivatives, fluorescein derivatives, tetracene derivatives, quinacridone derivatives, stilbene derivatives, distyryl arylene derivatives, tristyryl arylene derivatives, anthracene derivatives, berylline derivatives, coronene derivatives, dicyanomethylene pyran derivatives, dicyanomethylene thiopyran derivatives, cyanine derivatives or oxadine derivatives.

In some embodiments, the polymer can be a polylipid. The polylipid can include a phospholipid. The phospholipid can be a palmitoyl phospholipid. The palmitoyl phospholipid can be, for example, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(lauroyl).

In some embodiments, the polymer can be polyvinylpyrrolidone, a poly(ethylene oxide), a poly(ethylene oxide)-poly(propylene oxide)-poly (ethylene oxide) block co-polymer, poly (N-isopropyl acrylamide), polyethyleneimine, polyacrylamide, polyvinyl alcohol or collagen.

In some embodiments, the analyte can be a small molecule, protein, biomolecule, explosive, drug, biologic, or a metabolite thereof. For example, the analyte can be a monosaccharide, a polysaccharide, an amino acid, a nucleotide, an oligonucleotide, a lipid, a polylipid or a steroid. In other embodiments, the analyte can be a peptide or a protein. In some embodiments, the analyte can be riboflavin or nitric oxide. In some embodiments, the analyte can be 17-α-estradiol, 2,4-dinitrophenol, acetylcholine chloride, α-tocopherol, adenosine, adenosine-5′-triphosphate, cyclic adenosine monophosphate, creatinine, cytidine, D-aspartic acid, D-fructose, D-galactose, D-glucose, D-mannose, dopamine, glycine, guanosine, histamine, L-ascorbic acid, L-citrulline, L-histidine, L-thyroxine, melatonin, NADH, quinine, salicylic acid, serotonin, sodium azide, sodium pyruvate, sucrose, thymidine, tryptophan, tyramin or urea. In some embodiments, the analyte can be a DNA sequence, a RNA sequence or a siRNA sequence.

In some embodiments, the composition can further include an amount of the analyte. In some embodiments, the analyte can be a therapeutic.

In some embodiments, the sample can include a gas, a liquid or a solid. In some embodiments, the sample can be a biological fluid.

In some embodiments, the property can be an emission. In some embodiments, the property can be an emission intensity or an emission wavelength.

In some embodiments, exposing the composition to a sample can include inserting the composition into an animal. In some embodiments, the animal can be a human. In other embodiments exposing the composition to a sample can include inserting the composition into a plant or fungus. In some embodiments, exposing the composition to a sample can include incubating the composition with a microorganism or a virus. In some embodiments, exposing the composition to a sample can include incubating the composition with a cell line. In other embodiments, exposing the composition to a sample can include incubating the composition with an in vitro model system.

In some embodiments, determining the presence of an analyte can include determining the absence of the analyte. In other embodiments, determining the presence of an analyte can include determining the concentration of the analyte, determining the purity of an analyte or determining a quantity of an analyte.

In some embodiments, the method for analyzing a sample for an analyte can further include obtaining a sample. In other embodiments, the method for analyzing a sample for an analyte can further include obtaining a sample from an animal. In some embodiments, the animal can be a human. In some embodiments, the method for analyzing a sample for an analyte can further include obtaining a sample from a microorganism or virus. In some embodiments, the method for analyzing a sample for an analyte can further include obtaining a sample from a plant or fungus. In other embodiments, the method for analyzing a sample for an analyte can further include obtaining a sample from a cell line.

In some embodiments, the method for analyzing a sample for an analyte can further include coating a glass slide with the composition.

In another aspect, a method can include providing a composition which can include a complex, where the complex can include a nanostructure and a polymer, the polymer adsorbed on the nanostructure and the polymer being free from selective binding to an analyte in the absence of being adsorbed on the nanostructure, and a selective binding site associated with the complex, exposing the composition to a mixture containing the analyte, and separating the composition from the mixture, thereby removing the analyte from the mixture.

In some embodiments, the nanostructure can be a photoluminescent nanostructure.

In another aspect, a method can include providing a composition which can include a complex, where the complex can include a nanostructure and a polymer, the polymer adsorbed on the nanostructure and the polymer being free from selective binding to an analyte in the absence of being adsorbed on the nanostructure, and a selective binding site associated with the complex and an amount of the analyte, where the analyte can be a therapeutic, and administering the composition to an animal.

In some embodiments, the nanostructure can be a photoluminescent nanostructure.

In some embodiments, the method can further include monitoring a property of the composition and determining the presence of the therapeutic in the composition based on the property.

In some embodiments, monitoring a property of the composition can be performed using a high-throughput system. In other embodiments, the composition can be exposed to a sample in a well in a well plate array.

In another aspect, a method for analyzing samples in a high-throughput system, can include providing an array of compositions, wherein each composition includes a complex, wherein the complex includes a nanostructure, and a polymer, the polymer adsorbed on the nanostructure and the polymer being free from selective binding to an analyte in the absence of being adsorbed on the nanostructure; and a selective binding site associated with the complex; exposing each composition to at least one sample; monitoring a property of each composition; and determining the presence of an analyte in the sample based on the property.

In another aspect, a method can include providing a composition which can include a complex, where the complex can include a nanostructure and a polymer, the polymer adsorbed on the nanostructure and the polymer being free from selective binding to an analyte in the absence of being adsorbed on the nanostructure, and a selective binding site associated with the complex and an amount of the analyte, and exposing the composition to a catalyst.

In some embodiments, the nanostructure can be a photoluminescent nanostructure.

In some embodiments, the method can further include monitoring a property of the composition and determining modification of the analyte based on the property.

Other embodiments are within the claims.

