WO2021178923A1 - Devices and methods for detecting a target analyte of interest - Google Patents

Abstract

The invention relates generally to a sensor for detecting an analyte of interest in a sample including a CRISPR system that cleaves a target nucleic acid sequence when the analyte contacts the sensor, thereby producing a detectable signal indicative of the presence of the analyte.

Description

DEVICES AND METHODS FOR DETECTING A TARGET ANALYTE OF INTEREST Cross-Reference to Related Applications [0001] This application claims priority to and the benefit of U.S. Provisional Patent Application Number 62/986,207, which was filed on March 6, 2020, and U.S. Provisional Patent Application Number 63/048,273, which was filed on July 6, 2020, the disclosures of which are incorporated herein by reference in their entireties. Field of the Invention [0002] The invention relates generally to devices and methods for the detection of analytes in a sample. Background of the Invention [0003] The ability to rapidly detect trace amounts of analytes without the need for complicated or expensive equipment and without highly trained technicians is a capability that is highly sought across multiple industries, including health care, agriculture, environmental, defense, law enforcement, and many others. Point-of-care (POC) diagnostics in particular is one of the fastest growing markets in life sciences, with the benefits including quick and efficient testing and the abilities to reach more patients, eliminate follow-up visits, and ultimately save money and lives in the healthcare system. POC diagnostics have many direct applications in hospital systems, pharmacies, critical care settings, mobile settings, and resource-limited settings. [0004] Current state of the art techniques include the enzyme-linked immunoassay (ELISA), lateral flow immunoassay (LFA), and ribonucleic acid (RNA) based diagnostics, such as real- time reverse transcription polymerase chain reaction (RT-PCR). Most ELISA and RNA tests, however, are not truly POC formats, as they require specialized laboratories with extraordinary resources and staffed with highly trained technicians to run the tests and interpret the results. Even RNA tests that are characterized as POC tests require PCR amplification and a hand-held electrical device for signal readout and interpretation, making such tests impractical for widespread usage. As for LFAs, even though they require a POC format, they often have reliability issues, lack in robustness and, moreover, often are limited to applications that utilize antibodies. [0005] Therefore, a need exists across several fields for a novel, rapid, easy to use, and reliable analyte detection device. Summary of the Invention [0006] The invention is based, in part, upon the discovery of sensors that utilize the nucleic acid binding and nuclease activities of a CRISPR system to mediate the release of a reporter from a sensor in the presence of an analyte, thereby producing a detectable signal indicative of the presence of the analyte. It is contemplated that the sensors disclosed herein can be used as rapid, point-of-care sensors to assist, for example, in the identification, assessment and treatment of various medical conditions (when used by healthcare practitioners or other individuals in clinical or non-clinical settings), environmental monitoring, drug detection, or explosive detection. [0007] In one aspect, the invention provides a sensor for detecting an analyte of interest in a sample (e.g., a fluid sample). The sensor comprises: (a) a surface associated with a ribonucleoprotein (RNP) complex comprising (i) a CRISPR associated (Cas) nuclease; and (ii) a guide RNA (gRNA) comprising a region that binds to the Cas nuclease, and a region that is complementary to an activating nucleic acid sequence; and (b) a surface associated with a reporter that is tethered (e.g., covalently bound) to the surface by a nucleic acid linker comprising a target nucleic acid sequence. The sensor is configured such that, when the analyte contacts the sensor, the guide RNA binds to the activating nucleic acid, and the RNP complex cleaves the target nucleic acid sequence, thereby releasing the reporter and producing a detectable signal indicative of the presence of the analyte. [0008] In one embodiment, the reporter is part of an indicator where the release of the reporter via the RNP complex destroys at least a portion of a physical structure of the indicator. The indicator may be, for example, a structural color indicator. In another embodiment, the release of the reporter causes a change in a surface property of the surface associated with the reporter. For example, the surface associated with the reporter may change from a hydrophobic surface to a hydrophilic surface, or generally become more hydrophilic. [0009] In certain embodiments, the reporter is tethered (e.g., covalently bound) to the surface by one or more nucleic acid linkers comprising one or more target nucleic acid sequences. In certain embodiments, the one or more nucleic acid linkers are cross-linked. In certain embodiments, the one or more linkers (e.g., cross-linked linkers) link the reporter to the surface to form the indicator (e.g., structural color indicator), and optionally, the one or more linkers (e.g., cross-linked linkers) link the reporter and/or the surface to any other components required to form the indicator (e.g., structural color indicator). [0010] In certain embodiments, the activating nucleic acid is single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), or RNA. In certain embodiments, the target nucleic acid is single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), or RNA. [0011] In certain embodiments, the Cas nuclease is a type V Cas nuclease, for example, a Cas12a (Cpf1), Cas12b (C2c1), Cas12d, Cas12f (Cas14), or Cas12g nuclease. In certain embodiments, the Cas nuclease is a type VI Cas nuclease, for example, a Cas13a (C2c2), Cas13b, or Cas13d nuclease. [0012] In certain embodiments, the sensor further comprises: (c) a surface associated with an analyte binding agent (e.g., an aptamer or riboswitch) that binds to the analyte. Upon binding the analyte, the analyte binding agent induces the enzymatic activity of the RNP complex to cleave the target nucleic acid sequence. [0013] In certain embodiments, the analyte is a nucleic acid comprising the activating nucleic acid sequence. In certain embodiments, the analyte binding agent (e.g., aptamer or riboswitch) comprises the activating nucleic acid sequence. In certain embodiments, the sensor further comprises: (d) a surface associated with a nucleic acid including the activating nucleic acid sequence. [0014] In certain embodiments, upon binding of the analyte to the analyte binding agent (e.g., aptamer or riboswitch), the activating nucleic acid sequence is exposed for binding to the gRNA. [0015] In certain embodiments, the surface associated with the RNP complex and the surface associated with the reporter are the same surface. In certain embodiments, the surface associated with the RNP complex and the surface associated with the reporter are different surfaces (e.g., are spaced apart from one another). In certain embodiments, the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the analyte binding agent (e.g., aptamer or riboswitch) are the same surface. In certain embodiments, the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the analyte binding agent (e.g., aptamer or riboswitch) are different surfaces (e.g., are spaced apart from one another). [0016] In certain embodiments, the RNP complex is tethered (e.g., covalently bound) to the surface by a nucleic acid linker. In certain embodiments, the nucleic acid linker does not comprise the target nucleic acid sequence, in other embodiments, the nucleic acid linker does comprise the target nucleic acid sequence. In certain embodiments, the RNP complex is disposed within a hydrogel that is associated with the surface. [0017] In certain embodiments, the reporter comprises a hydrophobic moiety, that, for example, produces a visually detectable change, a detectable surface property change, or a detectable color change upon release. In certain embodiments, the reporter comprises a nanoparticle moiety, that, for example, produces a detectable color change upon release. In certain embodiments, the reporter comprises a redox tag. In certain embodiments, the reporter comprises a Raman tag. In certain embodiments, the reporter comprises a fluorophore. [0018] In certain embodiments, the sensor is disposed upon or integrated within a surface of a fluid receptacle or a straw. [0019] In certain embodiments, the analyte is selected from a metal ion, a small molecule, a protein, or a nucleic acid. In certain embodiments, the analyte is selected from a narcotic drug, an opioid, a date rape drug, ions (e.g., lead (Pb) ions), a biomarker (e.g., circulating cardiac troponin), an allergen (e.g., Ara h 1), an aflatoxin, and a viral, fungal, or bacterial nucleic acid sequence (e.g., a Zika virus or Dengue virus nucleic acid sequence). [0020] In certain embodiments, the sensor comprises two or more different RNP complexes comprising two or more different gRNAs. [0021] In another aspect, the invention provides a sensor for detecting an analyte of interest in a sample (e.g., a fluid sample). The sensor comprises a surface associated with a reporter that is tethered (e.g., covalently bound) to the surface by a nucleic acid linker comprising a target nucleic acid sequence. The sensor is configured such that, when the surface is contacted with (a) the analyte, and (b) a ribonucleoprotein (RNP) complex comprising (i) a CRISPR associated (Cas) nuclease; and (ii) a guide RNA (gRNA) comprising a region that binds to the Cas nuclease, and a region that is complementary to an activating nucleic acid sequence, the guide RNA binds to the activating nucleic acid, and the RNP complex cleaves the target nucleic acid sequence, thereby releasing the reporter and producing a detectable signal indicative of the presence of the analyte. In certain embodiments, the sensor is incubated with a solution including the RNP complex, for example, before, during, or after the sensor is contacted with the analyte. [0022] In another aspect, the invention provides a method for detecting an analyte of interest in a sample (e.g., a fluid sample). The method comprises contacting any of the foregoing sensors with the sample, and detecting a signal resulting from cleavage of a nucleic acid linker or cross-linked nucleic acid linker including the target nucleic acid sequence by the RNP complex. [0023] In another aspect, the invention provides a method for detecting an analyte of interest in a sample (e.g., a fluid sample). The method comprises contacting a sensor comprising a surface associated with a reporter that is tethered (e.g., covalently bound) to the surface by a nucleic acid linker comprising a target nucleic acid sequence with (a) the sample, and (b) a ribonucleoprotein (RNP) complex comprising (i) a CRISPR associated (Cas) nuclease; and (ii) a guide RNA (gRNA) comprising a region that binds to the Cas nuclease, and a region that is complementary to an activating nucleic acid sequence, such that the guide RNA binds to the activating nucleic acid, and the RNP complex cleaves the target nucleic acid sequence, thereby releasing the reporter and producing a detectable signal indicative of the presence of the analyte. In certain embodiments, the sensor is incubated with a solution including the RNP complex, for example, before, during, or after the sensor is contacted with the analyte. Brief Description of the Drawings [0024] In the drawings, like reference characters generally refer to the same parts throughout the different views. For the purposes of clarity, not every component may be labeled in every drawing. Also, the drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. In the following description, various embodiments of the present invention are described with reference to the following drawings, in which: [0025] FIGURE 1 depicts an exemplary sensor 101 including a separate sensing pad 102 (associated with a reporter) and CRISPR pad 103 (associated with one or more components of a CRISPR system); [0026] FIGURE 2A depicts an exemplary sensor 201 including a combined sensing and CRISPR pad 202 (associated with both and a reporter and one or more components of a CRISPR system); [0027] FIGURE 2B is a schematic depiction of the combined sensing and CRISPR pad 202 shown in FIGURE 2A; [0028] FIGURE 3A depicts an exemplary sensor 300 including an RNP complex 302 tethered to a surface of the sensor by a nucleic acid linker 303; [0029] FIGURE 3B depicts an exemplary sensor 304 including an RNP complex 305 associated with a water-soluble layer of poly-ethylene-glycol (PEG) or trehalose 306 on a surface of the sensor; [0030] FIGURE 3C depicts ssDNA, dsDNA, or RNA mediated activation of the RNP complexes in the sensors depicted in FIGURE 3A or 3B; [0031] FIGURE 4A depicts an exemplary sensor 401 including a layer of hydrogel 403 containing the RNP complex 402; [0032] FIGURE 4B depicts an exemplary sensor 407 including a layer of hydrogel 409 containing both the RNP complex 408 and the reporter 411; [0033] FIGURE 5A depicts an exemplary sensor that is in a sample fluid for analyte detection; [0034] FIGURE 5B depicts an exemplary sensor that is washed with a sample fluid, incubated with a sample fluid, and/or submerged in a sample fluid for analyte detection; [0035] FIGURE 6 depicts an exemplary method for analyte detection employing an analyte- binding agent 601 (e.g., aptamer or riboswitch); [0036] FIGURE 7 depicts an exemplary method for analyte detection employing an analyte- binding agent 701 (e.g., aptamer or riboswitch); [0037] FIGURE 8A depicts an exemplary gRNA 801 including a blocker and analyte- binding agent (e.g., aptamer or riboswitch); [0038] FIGURE 8B depicts the gRNA of FIGURE 8A in the absence of an analyte; [0039] FIGURE 8C depicts the gRNA of FIGURE 8A in the presence of an analyte; [0040] FIGURE 8D depicts an exemplary sensor 805 including the gRNA of FIGURE 8A; [0041] FIGURE 8E depicts the conformational change in the gRNA, and the resulting activation of the RNP, when the sensor of FIGURE 8D is contacted with an analyte of interest; [0042] FIGURE 9 depicts an exemplary sensor 900 comprising a solid support 901 having disposed separately thereon, an analyte-binding agent (e.g., aptamer or riboswitch) and activating DNA pad 902 (associated with a DNA duplex including an analyte-binding agent (e.g., aptamer or riboswitch) and complementary activating DNA sequence), a gRNA pad 903 (associated with a CRISPR gRNA), a Cas nuclease pad 904 (associated with a CRISPR Cas nuclease) and a sensing pad 905 (associated with a reporter); [0043] FIGURE 10 is a depiction of RNP complexes including three different guide RNAs in an exemplary sensor (guide 1, guide 2, and guide 3) binding to three different nucleic acid sequences within a DNA analyte; [0044] FIGURE 11A depicts a surface property sensor 1100, in accordance with one embodiment of the invention; [0045] FIGURE 11B depicts the surface property sensor of FIGURE 11A, in which the nucleic acid (e.g., DNA) linkers have been cleaved; [0046] FIGURE 12A depicts a structural color sensor 1200, in accordance with one embodiment of the invention; [0047] FIGURE 12B depicts the structural color sensor of FIGURE 12A, in which the DNA linkers have been cleaved; [0048] FIGURE 13A depicts a structural color sensor under a hydrophobic condition, in accordance with one embodiment of the invention; [0049] FIGURE 13B depicts a structural color sensor under a hydrophilic condition, in accordance with one embodiment of the invention; [0050] FIGURE 14 depicts a flow chart for manufacturing the structural color sensor of FIGURE 12A, in accordance with one embodiment of the invention; [0051] FIGURE 15A depicts a structural color sensor 1500, in accordance with one embodiment of the invention; [0052] FIGURE 15B depicts the structural color sensor of FIGURE 15A, in which the DNA linkers have been cleaved; [0053] FIGURE 16A depicts a structural color sensor 1600, in accordance with one embodiment of the invention; [0054] FIGURE 16B depicts the structural color sensor of FIGURE 16A, in which the DNA linkers have been cleaved; [0055] FIGURE 17 depicts a structural color sensor and an RNP complex located together on the same pad, in accordance with one embodiment of the invention; [0056] FIGURE 18A depicts a sensor 1800 for generating an electrical readout, in accordance with one embodiment of the invention; [0057] FIGURE 18B depicts the sensor of FIGURE 18A, in which the DNA linkers have been cleaved; [0058] FIGURE 19A depicts a sensor 1900 for generating an optical readout, in accordance with one embodiment of the invention; and [0059] FIGURE 19B depicts the sensor of FIGURE 19A, in which the DNA linkers have been cleaved. Detailed Description [0060] To provide an overall understanding of the invention, certain illustrative embodiments will now be described, including devices, methods of making the devices, and methods of detecting an analyte target molecule of interest in a fluid sample. However, the devices and methods described herein may be adapted and modified as appropriate for the application being addressed and the devices and methods described herein may be employed in other suitable applications. All such adaptations and modifications are to be considered within the scope of the invention. [0061] Throughout the description, where compositions and devices such as a sensor are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions and devices of the present disclosure that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present disclosure that consist essentially of, or consist of, the recited processing steps. [0062] In the application, where an element or component is said to be included in and/or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components. [0063] Further, it should be understood that elements and/or features of a device or a method described herein can be combined in a variety of ways without departing from the spirit and scope of the present disclosure, whether explicit or implicit herein. For example, where reference is made to a particular feature, that feature can be used in various embodiments of the devices of the present disclosure and/or in methods of the present disclosure, unless otherwise understood from the context. In other words, within this application, embodiments have been described and depicted in a way that enables a clear and concise application to be written and drawn, but it is intended and will be appreciated that embodiments can be variously combined or separated without parting from the present teachings and disclosure(s). For example, it will be appreciated that all features described and depicted herein can be applicable to all aspects of the disclosure(s) described and depicted herein. [0064] The articles “a” and “an” are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article, unless the context is inappropriate. By way of example, “an element” means one element or more than one element. [0065] The term and/or is used in this disclosure to mean either and or or unless indicated otherwise. [0066] It should be understood that the expression “at least one of” includes individually each of the recited objects after the expression and the various combinations of two or more of the recited objects unless otherwise understood from the context and use. The expression “and/or” in connection with three or more recited objects should be understood to have the same meaning unless otherwise understood from the context. [0067] The use of the term “include,” “includes,” “including,” “have,” “has,” “having,” “contain,” “contains,” or “containing,” including grammatical equivalents thereof, should be understood generally as open-ended and non-limiting, for example, not excluding additional unrecited elements or steps, unless otherwise specifically stated or understood from the context. [0068] Where the use of the term “about” is before a quantitative value, the present disclosure also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ±10% variation from the nominal value unless otherwise indicated or inferred. [0069] Where a percentage is provided with respect to an amount of a component or material in a composition such as a polymer, the percentage should be understood to be a percentage based on weight, unless otherwise stated or understood from the context. [0070] Where a molecular weight is provided and not an absolute value, for example, of a polymer, then the molecular weight should be understood to be an average molecule weight, unless otherwise stated or understood from the context. [0071] It should be understood that the order of steps or order for performing certain actions is immaterial so long as the present disclosure remains operable. Moreover, two or more steps or actions can be conducted simultaneously. [0072] At various places in the present specification, features are disclosed in groups or in ranges. It is specifically intended that the description include each and every individual subcombination of the members of such groups and ranges. For example, an integer in the range of 0 to 40 is specifically intended to individually disclose 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, and 40, and an integer in the range of 1 to 20 is specifically intended to individually disclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. [0073] The use of any and all examples, or exemplary language herein, for example, such as” or “including,” is intended merely to illustrate better the present disclosure and does not pose a limitation on the scope of the disclosure unless claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the present disclosure. [0074] Various aspects of the disclosure are set forth herein under headings and/or in sections for clarity; however, it is understood that all aspects, embodiments, or features of the disclosure described in one particular section are not to be limited to that particular section but rather can apply to any aspect, embodiment, or feature of the present disclosure. CRISPR-Based Sensors [0075] Among other things, the invention provides a sensor for detecting an analyte of interest in a sample (e.g., a fluid sample). The sensor comprises one or more surfaces associated with a CRISPR system (e.g., having trans-cleavage activity) or a component thereof, and one or more surfaces associated with a reporter. The reporter is tethered to the surface by a linker (e.g., a nucleic acid linker, e.g., a DNA linker). The sensor is configured such that, when the analyte contacts the sensor, the CRISPR system cleaves the linker, thereby releasing the reporter and producing a detectable signal indicative of the presence of the analyte. In certain embodiments, when the analyte contacts the sensor, an activating nucleic acid binds to the CRISPR system, triggering cleavage of the linker and release of the reporter. In certain embodiments, wherein the analyte is a nucleic acid (e.g., ssDNA, dsDNA, or RNA), the analyte includes the activating nucleic acid and therefore can directly activate the CRISPR system. In certain embodiments, the analyte does not include the activating nucleic acid (and may be, e.g., a small molecule or a protein) but the presence of the analyte mediates the availability or binding of the activating nucleic acid, and therefore can indirectly activate the CRISPR system. [0076] In one embodiment, the reporter is part of a structural color indicator and release of the reporter destroys at least a portion of the structural color indicator, thereby leading to a color change. Alternatively, in another embodiment, the release of the reporter causes a change in a surface property of the surface associated with the reporter. For example, the surface associated with the reporter may change from hydrophobic to hydrophilic, or change from a surface that is hydrophobic to a surface that is more hydrophilic, thereby allowing the infiltration of fluid into a colorimetric indicator and to a consequent change in color. It is also contemplated that the signal may be developed or detected in a fluid sample following contact with the sensor, for example as a result of the reporter being released into the fluid. The signal may include, for example, a change in a physical property (e.g., photon absorption or emission) of the fluid. [0077] CRISPR systems typically include: (i) a CRISPR associated (Cas) nuclease; and (ii) a guide polynucleotide (e.g., a guide RNA (gRNA)). Two distinct classes of CRISPR-Cas systems have been identified. Class 1 CRISPR-Cas systems utilize multi-protein effector complexes, whereas class 2 CRISPR-Cas systems utilize single-protein effectors (see, Makarova et al. (2017) CELL, 168: 328). Among the three types of class 2 CRISPR-Cas systems, type II and type V systems typically target DNA and type VI systems typically target RNA (id.). Naturally occurring type II effector complexes consist of Cas9, CRISPR RNA (crRNA), and trans- activating CRISPR RNA (tracrRNA), but the crRNA and tracrRNA can be fused as a single guide RNA in an engineered system for simplicity (see, Wang et al. (2016) ANNU. REV. BIOCHEM., 85: 227). Certain naturally occurring type V or VI systems, such as type V-A, type V-C, and type V-D systems, do not require tracrRNA and use crRNA alone as the guide for cleavage of target DNA (see, Zetsche et al. (2015) CELL, 163: 759; Makarova et al. (2017) CELL, 168: 328). The terms “CRISPR system” and “CRISPR RNP complex” are used interchangeably herein, unless indicated otherwise. [0078] As used herein, the terms “CRISPR-Associated protein,” “Cas protein,” “Cas nuclease” and “Cas,” refer to a Cas protein derived from any species, subspecies, or strain of bacteria that encodes the Cas protein of interest, as well as variants and orthologs of the particular Cas protein in question. Non-limiting examples of Cas proteins include Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Cas10, Cas12a, Cas12b, Cas12d, Cas12f (Cas14), Cas12g, Cas13a, Cas13b, Cas13d, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx15, Csf1, Csf2, Csf3, Csf4, C2C1, C2C2, C2C3, CASCADE, homologs thereof, and modified versions thereof. [0079] In certain embodiments, the Cas nuclease is a type V Cas nuclease (for example, according to the classification described in Makarova et al. (2017) CELL, 168: 328). For example, the Cas nuclease may be a Cas12a (Cpf1), Cas12b (C2c1), Cas12d, Cas12f (Cas14), or Cas12g nuclease. In certain embodiments, the Cas nuclease is a type VI Cas nuclease, for example, a Cas13a (C2c2), Cas13b, or Cas13d nuclease. [0080] As used herein, the term “guide polynucleotide” refers to one or more polynucleotides that guide a protein, such as a Cas nuclease, to bind to a target nucleic acid. Guide polynucleotides can comprise ribonucleotide bases (e.g., RNA); deoxyribonucleotide bases (e.g., DNA); and combinations of ribonucleotide bases and deoxyribonucleotide bases (e.g., RNA/DNA chimeric molecules); nucleotides; nucleotide analogs; modified nucleotides; and the like; as well as synthetic, naturally occurring, and non-naturally occurring modified backbone residues or linkages. In certain embodiments, a guide polynucleotide is a guide RNA (gRNA). In certain embodiments, a gRNA comprises a crRNA and a tracrRNA (separately, or fused as a single guide RNA). In embodiments, a gRNA comprises a crRNA. [0081] While some CRISPR systems only specifically cleave target nucleic acid that is complementary to the gRNA and are therefore employed for genome editing, other CRISPR systems become activated for non-specific target nucleic acid cleavage or “trans-cleavage” (also referred to as collateral cleavage) when bound to a nucleic acid that is complementary to the gRNA. In certain embodiments, a CRISPR system has trans-cleavage activity, i.e., the CRISPR system can non-specifically cleave target nucleic acid when bound to an activating nucleic acid that is complementary to the gRNA of the CRISPR system. Exemplary CRISPR systems with trans-cleavage activity include CRISPR systems comprising the type V Cas12 nucleases or the type VI Cas13 nucleases, which are known to exhibit non-specific trans-cleavage of target nucleic acids (including DNA and/or RNA). [0082] Certain CRISPR systems include accessory proteins that enhance or otherwise regulate the activity of the CRISPR system (for example, WYL1 as described in Yan et al. (2018) MOL. CELL 70(2):327-339). Throughout the specification and claims, where reference is made to CRISPR system or RNP complex including a Cas nuclease and a gRNA, it is understood that the CRISPR system or RNP complex may further include one or more appropriate accessory proteins. [0083] Exemplary CRISPR systems, including CRISPR systems with trans-cleavage activity, are described in Nguyen et al. (2020) NATURE COMMUNICATIONS 11: 4906; Li et al. (2018) CELL RESEARCH 28: 491–493; Fuchs et al. (2019) bioRxiv doi: 10.1101/600890; Chen et al. (2018) SCIENCE 360, 6387: 436-439; Yan et al. (2019) SCIENCE 363, 6422: 88-91; Harrington et al. (2018) SCIENCE 362, 6416: 839-842; Abudayyeh et al. (2016) SCIENCE 353, 6299:aaf5573. [0084] In certain embodiments, the activating nucleic acid is single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), or RNA. In certain embodiments, the target nucleic acid is single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), or RNA. [0085] It is contemplated that each of the CRISPR system or RNP complex components (e.g., the Cas nuclease and the gRNA) and the reporter may be associated with any appropriate surface within the sensor. For example, in certain embodiments, the surface associated with the RNP complex and the surface associated with the reporter are the same surface. In certain embodiments, the surface associated with the RNP complex and the surface associated with the reporter are different surfaces (e.g., are spaced apart from one another). [0086] For example, FIGURE 1 depicts a sensor 101 including a solid strip including a separate sensing pad or surface 102 (associated with a reporter) and a CRISPR pad or surface 103 (associated with a CRISPR RNP complex including a Cas nuclease and gRNA, or a component thereof). The sensing pad 102 and CRISPR pad 103 may be separated apart by a distance L 104. In certain embodiments, each of the reporter and the RNP complex (or at least portion of each) are associated with (e.g., immobilized on) the solid strip. In certain embodiments, when an analyte of interest contacts the sensor, cleavage of a linker by the RNP complex releases the reporter and produces a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte. In certain embodiments, detection of the analyte using the sensor requires no additional reagents and/or mixing steps. FIGURE 2A depicts an additional exemplary sensor 201 including a combined sensing and CRISPR pad or surface 202. FIGURE 2B depicts an enlarged, schematic representation of the combined sensing and CRISPR pad or surface 202 shown in FIGURE 2A. The same pad is associated with both the reporter 203 (including, e.g., a hydrophobic moiety) and the CRISPR RNP complex 204 (or a component thereof). [0087] It is contemplated that a CRISPR system or RNP complex, or the components thereof (e.g., the Cas nuclease and the gRNA) may be associated with a surface of the sensor by any appropriate means, including, for example, physical or chemical immobilization. [0088] For example, in certain embodiments, the RNP complex is tethered (e.g., covalently bound) to a surface by a nucleic acid linker, for example, a nucleic acid linker comprising the target nucleic acid sequence. [0089] For example, FIGURE 3A depicts a sensor 300 including a CRISPR pad or surface 301 (associated with a CRISPR RNP complex 302, including a Cas nuclease and gRNA). In certain embodiments, the RNP complex 302 has trans-cleavage activity. The RNP complex 302 (or at least portion thereof) is tethered (e.g., covalently bound) to the surface by a nucleic acid linker 303. In certain embodiments, the nucleic acid linker 303 does not include a target nucleic acid sequence that is capable of being cleaved by the RNP complex. The sensor may also include, for example, a reporter that is tethered to a surface of the sensor by a nucleic acid linker that is capable of being cleaved by the RNP complex (not shown in FIGURE 3A). [0090] Another exemplary sensor includes a CRISPR pad or surface (associated with a CRISPR RNP complex, including a Cas nuclease and gRNA). In certain embodiments, the RNP complex has trans-cleavage activity. The RNP complex (or at least portion thereof) is tethered (e.g., covalently bound) to the surface by a nucleic acid linker. The nucleic acid linker may be, for example, a short DNA oligomer or any other linker that is capable of being nonspecifically or specifically cleaved by the RNP complex, e.g., a linker including a phosphodiester bond. In certain embodiments, the linker may include hybridized DNA strands wherein a first strand of the DNA is associated with (e.g., covalently bound to) the RNP complex or a component thereof, and a second strand of the DNA is associated with (e.g., covalently bound to) the surface of the sensor. The sensor may also include, for example, a reporter that is tethered to a surface of the sensor, also by a nucleic acid linker that is capable of being cleaved by the RNP complex. In certain embodiments, when an analyte of interest (e.g., a nucleic acid, e.g., DNA (ssDNA or dsDNA) or RNA, including an activating nucleic acid sequence that is complementary to the gRNA in the RNP complex) contacts the sensor, the RNP complex first non-specifically (or specifically) cleaves the linker tethering itself to the surface, releasing the RNP complex from the surface of the sensor, and the RNP complex then non-specifically (or specifically) cleaves the linker tethering the reporter to the sensor surface, releasing the reporter from the surface of the sensor and producing a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte. [0091] FIGURE 3B depicts another exemplary sensor 304 including a CRISPR pad or surface 307 (associated with a CRISPR RNP complex 305, including a Cas nuclease and gRNA). In certain embodiments, the RNP complex 305 has trans-cleavage activity. In certain embodiments, the RNP complex 305 (or at least portion of each) is associated with the surface 304 by a Van der Waals force. For example, the RNP complex may be associated with a water- soluble layer of poly-ethylene-glycol (PEG) or trehalose 306 that is released from the substrate when a liquid sample is introduced for testing. The sensor may also include, for example, a reporter that is tethered to a surface of the sensor by a nucleic acid linker that is capable of being cleaved by the RNP complex (not shown in FIGURE 3B). [0092] FIGURE 3C depicts two types of activation of an RNP complex 307 (for example, the RNP complex depicted in FIGURE 3A or 3B) in a sensor. In a first embodiment, when dsDNA 308 including an activating nucleic acid sequence that is complementary to the gRNA in the RNP complex 307 contacts the sensor, the dsDNA 308 binds to the RNP complex 307 to produce an activated RNP complex 309. The activated RNP complex 309 non-specifically (or specifically) cleaves a linker tethering a reporter to the sensor surface, releasing the reporter from the surface of the sensor and producing a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte (not shown in FIGURE 3C). In a second embodiment, when ssDNA or RNA 310 including an activating nucleic acid sequence that is complementary to the gRNA in the RNP complex 307 contacts the sensor, the ssDNA or RNA 310 binds to the RNP complex 307 to produce an activated RNP complex 311. The activated RNP complex 311 non-specifically (or specifically) cleaves a linker tethering a reporter to the sensor surface, releasing the reporter from the surface of the sensor and producing a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte (not shown in FIGURE 3C). [0093] In certain embodiments, the RNP complex is disposed within a hydrogel (a polymer network swollen with water or solute containing, e.g., stabilizing reagents) that is associated a surface of the sensor. For example, FIGURE 4A depicts a sensor 401 including a CRISPR system or RNP complex 402 maintained in a hydrogel 403. In certain embodiments, when an analyte of interest contacts the sensor, cleavage of a linker 404 by the RNP complex 402 releases an otherwise immobilized reporter 405 and produces a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte. It is contemplated that the RNP complex 402 may, for example, diffuse from the layer of hydrogel into an area containing the immobilized reporter 406. FIGURE 4B depicts a sensor 407 including a CRISPR system or RNP complex 408 maintained in a hydrogel 409. In certain embodiments, when an analyte of interest contacts the sensor, cleavage of a linker 410 by the RNP complex 408 releases an otherwise immobilized reporter 411 and produces a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte. It is contemplated that the sensor may include the RNP complex 408 and reporter 411 in the same hydrogel 409. [0094] It is contemplated that a nucleic acid (e.g., DNA) linker (for example, linking a reporter to a surface of the sensor or linking a CRISPR system or RNP complex or component thereof to a surface of the sensor) may be associated with a surface of sensor, a reporter, or a CRISPR system or component thereof by any appropriate means. For example, a nucleic acid (e.g., DNA) linker may be covalently attached to a surface, reporter, or CRISPR system by NHS-EDC coupling chemistry, glutaraldehyde mediated coupling chemistry, or click chemistry such as Copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC), [0095] Sensors disclosed herein may be used in any appropriate format, which may depend upon how the CRISPR RNP complex (or component thereof) and/or the reporter are associated with the sensor. For example, as shown in FIGURE 5, a sensor may include, or be disposed upon, a strip. As shown in FIGURE 5A, in certain embodiments (for example, where the RNP complex is immobilized on a surface of the strip) the strip 501 may be kept in a sample fluid 502 (e.g., submerged in the sample fluid) until detection of the analyte. As shown in FIGURE 5B, in certain embodiments (for example, where the RNP complex is contained in a solution that is, for example, added to the sample fluid and/or spotted on the surface of the strip) the strip 501 may be washed 503 with the sample fluid 502, incubated 504 with the sample fluid 520, or washed and submerged 505 in the sample fluid 502. Sensors disclosed herein may also be used, for example, in fluidic devices or in any other devices that contains a cavity or surface that contacts a fluid sample. [0096] Sensors disclosed herein may include an analyte-binding agent, for example, an aptamer or riboswitch. For example, in certain embodiments, the sensor further comprises: (c) a surface associated with an analyte-binding agent (e.g., a nucleic acid based binding agent, e.g., an aptamer or riboswitch) that binds to the analyte. Similarly, in certain embodiments, the sensor does not include a surface associated with the analyte-binding agent (e.g., aptamer or riboswitch), but a method of detecting an analyte using the sensor includes contacting the sensor and/or analyte with the analyte-binding agent (e.g., aptamer or riboswitch). [0097] Exemplary nucleic acid based binding agents include aptamers and spiegelmers. Aptamers are nucleic acid-based sequences that have strong binding activity for a specific target molecule. Spiegelmers are similar to aptamers with regard to binding affinities and functionality but have a structure that prevents enzymatic degradation, which is achieved by using nuclease resistant L-oligonucleotides rather than naturally occurring, nuclease sensitive D- oligonucleotides. [0098] Aptamers are specific nucleic acid sequences that bind to target molecules with high affinity and specificity and are identified by a method commonly known as Selective Evolution of Ligands by Evolution (SELEX), as described, for example, in U.S. Patent Nos.5,475,096 and 5,270,163. Each SELEX-identified nucleic acid ligand is a specific ligand of a given target compound or molecule. The SELEX process is based on the observation that nucleic acids have sufficient capacity for forming a variety of two- and three-dimensional structures and sufficient chemical versatility available within their monomers to act as ligands (form specific binding pairs) with virtually any chemical compound, whether monomeric or polymeric. Molecules of any size or composition can serve as targets. [0099] The SELEX method applied to the application of high affinity binding involves selection from a mixture of candidate oligonucleotides and step-wise iterations of binding, partitioning and amplification, using the same general selection scheme, to achieve virtually any desired criterion of binding affinity and selectivity. Starting from a mixture of nucleic acids, preferably comprising a segment of randomized sequence, the SELEX method includes steps of contacting the mixture with the target under conditions favorable for binding, partitioning unbound nucleic acids from those nucleic acids which have bound specifically to target molecules, dissociating the nucleic acid-target complexes, amplifying the nucleic acids dissociated from the nucleic acid-target complexes to yield a ligand enriched mixture of nucleic acids, then reiterating the steps of binding, partitioning, dissociating and amplifying through as many cycles as desired to yield highly specific high affinity nucleic acid ligands to the target molecule. Thus, this method allows for the screening of large random pools of nucleic acid molecules for a particular functionality, such as binding to a given target molecule. [0100] The SELEX method also encompasses the identification of high-affinity nucleic acid ligands containing modified nucleotides conferring improved characteristics on the ligand, such as improved in vivo stability and protease resistance. Examples of such modifications include chemical substitutions at the ribose and/or phosphate and/or base positions. SELEX process- identified nucleic acid ligands containing modified nucleotides are described in U.S. Patent Nos. 5,660,985 and 5,580,737, which include highly specific nucleic acid ligands containing one or more nucleotides modified at the 2’ position with, for example, a 2’-amino, 2’-fluoro, and/or 2’- O-methyl moiety. [0101] Instead of using aptamers, which may require additional modifications to become more resistant to nuclease activity, it is contemplated that spiegelmers, mirror image aptamers composed of L-ribose or L-2’deoxyribose units (see, U.S. Patent Nos.8,841,431, 8,691,784, 8367,629, 8,193,159 and 8,314,223) can be used in the practice of the invention. The chiral inversion in spiegelmers results in an improved plasma stability compared with natural D- oligonucleotide aptamers. L-nucleic acids are enantiomers of naturally occurring D-nucleic acids that are not very stable in aqueous solutions and in biological samples due to the widespread presence of nucleases. Naturally occurring nucleases, particularly nucleases from animal cells are not capable of degrading L-nucleic acids. [0102] Using in vitro selection, an oligonucleotide that binds to the synthetic enantiomer of a target molecule, e.g., a D-peptide, can be selected. The resulting aptamer is then resynthesized in the L-configuration to create a spiegelmer (from the German “spiegel” for mirror) that binds the physiological target with the same affinity and specificity as the original aptamer to the mirror-image target. This approach has been used to synthesize spiegelmers that bind, for example, hepcidin (see, U.S. Patent No.8,841,431), MCP-1 (see, U.S. Patent Nos.8,691,784, 8367,629 and 8,193,159) and SDF-1 (see, U.S. Patent No.8,314,223). [0103] Other aptamer-like structures contemplated for use as analyte-binding agents in the practice of the invention include, for example, any receptor whose binding sequence was determined from a selection iteration process based on a library of suitable building blocks. For example, an aptamer-like structure may be made from peptide nucleic acids via a SELEX process. Additional exemplary binding agents include riboswitches, Slow Off-rate Modified Aptamers (SOMAmers), or affimers. Other binding agents may be used as appropriate without departing from the scope of the disclosure. [0104] In certain embodiments, the sensor includes a surface associated with an analyte binding agent (e.g., aptamer or riboswitch) that comprises an activating nucleic acid sequence, or the sensor is contacted with an analyte binding agent (e.g., aptamer or riboswitch) that comprises an activating nucleic acid sequence, and binding of the analyte by the analyte binding agent exposes the activating nucleic acid sequence (for example, for binding to and activating an RNP complex). [0105] For example, FIGURE 6 depicts an exemplary method of analyte detection employing an analyte-binding agent 601. The analyte-binding binding agent 601 may be, for example, a nucleic acid based binding agent, e.g., an aptamer, an aptamer-like binding agent, or a riboswitch. The analyte 602 is not required to be a nucleic acid, and may be, for example a small molecule, protein, or cell. A sensor (i) includes a surface associated with a CRISPR system or RNP complex 603 (including a Cas nuclease and gRNA), (ii) includes a surface associated with a reporter (not shown in FIGURE 6), and (iii) either includes a surface associated with the analyte-binding agent 601 (e.g., aptamer or riboswitch) or is contacted with the analyte binding agent 601 (e.g., aptamer or riboswitch). In certain embodiments, when the analyte 602 contacts the sensor, the analyte binding agent 601 (e.g., aptamer or riboswitch) binds the analyte 602, resulting in a conformational change in the analyte binding agent that exposes an activating nucleic acid 604 (e.g., a partial ssDNA including a sequence that is complementary to the gRNA of the RNP complex). Binding of the activating nucleic acid 604 to the RNP complex 603 activates the RNP complex 603, resulting in cleavage (specific or non-specific cleavage) of a linker by the RNP complex, which releases the reporter and produces a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte (not shown in FIGURE 6). [0106] In certain embodiments, (i) the sensor includes a surface associated with a nucleic acid including the activating nucleic acid sequence, and (ii) the sensor includes a surface associated with an analyte binding agent (e.g., aptamer or riboswitch), or the sensor is contacted with an analyte binding agent (e.g., aptamer or riboswitch). In certain embodiments, in the absence of the analyte, the activating nucleic acid sequence is bound or otherwise occluded by the analyte binding agent (e.g., aptamer or riboswitch), and when the analyte contacts the sensor, the analyte binding agent (e.g., aptamer or riboswitch) instead binds to the analyte, exposing the activating nucleic acid sequence (for example, for binding to and activating an RNP complex). [0107] For example, FIGURE 7 depicts an exemplary method of analyte detection employing an analyte-binding agent 701. The analyte-binding agent 701 may be, for example, a nucleic acid based binding agent, e.g., an aptamer, aptamer-like binding agent, or riboswitch. The analyte 702 is not required to be a nucleic acid, and may be, for example a small molecule or protein macromolecule. A sensor including (i) a surface associated with a CRISPR system or RNP complex 703, including a Cas nuclease and gRNA, (ii) a surface associated with a reporter, and (not shown in FIGURE 7), and (iii) a surface associated with an activating nucleic acid sequence 704, either further includes a surface associated with the analyte-binding agent 701 (e.g., aptamer or riboswitch) or is contacted with the analyte binding agent 701 (e.g., aptamer or riboswitch). In certain embodiments, in the absence of the analyte 702, the activating nucleic acid sequence 704 is bound by the analyte binding agent 701 (e.g., aptamer or riboswitch). For example, the activating nucleic acid sequence 704 may hybridize to a complementary sequence in the analyte binding agent 701 (e.g., aptamer or riboswitch) to form a duplex. When the analyte 702 contacts the sensor, the analyte binding agent 701 (e.g., aptamer or riboswitch) instead binds to the analyte 702 (e.g., decoupling the duplex) exposing the activating nucleic acid sequence 704 for binding to the RNP complex 703. Binding of the activating nucleic acid 704 to the RNP complex 703 activates the RNP complex 703, resulting in cleavage (specific or non-specific cleavage) of a linker by the RNP complex 703, which releases the reporter and produces a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte (not shown in FIGURE 7). [0108] In certain embodiments, the analyte-binding agent (e.g., aptamer or riboswitch) is capable of binding to or otherwise occluding the gRNA. When the analyte contacts the sensor, the analyte binding agent (e.g., aptamer or riboswitch) instead binds to the analyte, exposing the gRNA (for example, for binding to an activating nucleic acid sequence). In certain embodiments, the analyte-binding agent (e.g., aptamer or riboswitch) and gRNA are included as part of a single nucleic acid molecule. [0109] For example, FIGURE 8A depicts an exemplary gRNA for use in analyte detection. In certain embodiments, the analyte-binding agent (e.g., aptamer or riboswitch) and gRNA are included as part of a single nucleic acid molecule. For example, the gRNA 801 may be modified via oligonucleotide synthesis to include a blocker sequence 802 and an analyte-binding aptamer or riboswitch sequence 803. In certain embodiments, as shown in FIGURE 8B, in the absence of the analyte, the gRNA 801 is prevented from forming a stable complex with the activating nucleic acid sequence and/or Cas nuclease. For example, the nucleic acid molecule may form a duplex. When the analyte 804 contacts the sensor, as shown in FIGURE 8C, the analyte binding agent 803 (e.g., aptamer or riboswitch) instead binds to the analyte 804 (e.g., decoupling the duplex) exposing the gRNA 801 for binding to an activating nucleic acid sequence. [0110] FIGURE 8D depicts an exemplary sensor 805 including the gRNA 806 of FIGURES 8A-8C. The sensor includes (i) a surface associated with a Cas nuclease 807, (ii) a surface associated with the gRNA 806 of FIGURES 8A-8C, (iii) a surface associated with a nucleic acid (e.g., DNA) including an activating nucleic acid sequence 808 (e.g., that is complementary to the gRNA), and (iv) a surface associated with a reporter (not shown in FIGURE 8D). In certain embodiments, in the absence of the analyte, the analyte binding agent (e.g., aptamer or riboswitch) of the gRNA hybridizes to the blocker sequence of the gRNA to form a duplex, preventing stable complex formation between the gRNA and the activating nucleic acid sequence and/or Cas nuclease. [0111] FIGURE 8E depicts an exemplary method of analyte detection employing the sensor of FIGURE 8D. In certain embodiments, in the absence of the analyte 804, the analyte binding agent 803 (e.g., aptamer or riboswitch) of the gRNA 801 hybridizes to the blocker sequence 802 of the gRNA 801 to form a duplex, preventing stable complex formation between the gRNA 801 and the activating nucleic acid sequence 808 and/or Cas nuclease 807. When the analyte 804 contacts the sensor, the analyte binding agent 803 (e.g., aptamer or riboswitch) instead binds to the analyte 804, decoupling the duplex between the blocker sequence 802 and gRNA 801, and allowing the gRNA 801 to bind to the activating nucleic acid sequence 808. Binding of the activating nucleic acid 808 to the gRNA 801 allows for formation of an active RNP complex, resulting in cleavage (specific or non-specific cleavage) of a linker by the RNP complex, which releases the reporter and produces a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte (not shown in FIGURE 8E). [0112] It is contemplated that, when a sensor includes an analyte binding agent (e.g., aptamer or riboswitch), each of the CRISPR system or RNP complex components (e.g., the Cas nuclease and the gRNA), the reporter, and the analyte binding agent (e.g., aptamer or riboswitch) may be associated with any appropriate surface within the sensor. For example, in certain embodiments, the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the analyte binding agent (e.g., aptamer or riboswitch) are the same surface. In certain embodiments, the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the analyte binding agent (e.g., aptamer or riboswitch) are different surfaces (e.g., are spaced apart from one another). [0113] Similarly, it is contemplated that, when a sensor includes a surface associated with the activating nucleic acid, each of the CRISPR system or RNP complex components (e.g., the Cas nuclease and the gRNA), the reporter, and the activating nucleic acid may be associated with any appropriate surface within the sensor. For example, in certain embodiments, the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the activating nucleic acid (e.g., DNA) are the same surface. In certain embodiments, the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the activating nucleic acid (e.g., DNA) are different surfaces (e.g., are spaced apart from one another). [0114] For example, FIGURE 9 depicts a sensor 900 including a solid support 901 including a separate analyte-binding agent (e.g., aptamer or riboswitch) and activating DNA pad 902 (associated with a DNA duplex including an analyte-binding agent (e.g., aptamer or riboswitch) and complementary activating DNA sequence), gRNA pad or surface 903 (associated with a CRISPR gRNA), Cas nuclease pad or surface 904 (associated with a CRISPR Cas nuclease), and sensing pad or surface 905 (associated with a reporter). In certain embodiments, each of the activating nucleic acid (e.g., DNA), gRNA, Cas nuclease, and reporter (or at least portion of each) are associated with (e.g., immobilized on) the solid support. It is also contemplated that one or more of the activating nucleic acid (e.g., DNA), gRNA, Cas nuclease, and reporter may also be spotted on a polymer brush surface, as described below. In certain embodiments, in the absence of the analyte, the activating DNA is bound by an analyte-binding agent (e.g., aptamer or riboswitch), and when an analyte of interest contacts the sensor, the analyte-binding agent instead binds to the analyte, freeing the activating nucleic acid (e.g., DNA) to bind the guide RNA of the RNP complex. Binding of the RNP complex by the activating nucleic acid sequence and resulting cleavage of a linker by the RNP complex releases the reporter and produces a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte (not shown in FIGURE 9). [0115] It is contemplated that a sensor may include one or more different CRISPR systems or RNP complexes. For example, a sensor may include two or more different gRNAs that each bind to (e.g., are complementary to) a different activating nucleic acid sequence. Similarly, a sensor may include two or more different Cas nucleases that may, for example, have different substrate specificities. [0116] For example, FIGURE 10 depicts an exemplary sensor including three CRISPR RNP complexes each including a different gRNA (guide 11001, guide 21002, and guide 31003). The sensor may include (i) a surface associated with the three RNP complexes and (ii) a surface associated with a reporter (not shown in FIGURE 10). In certain embodiments, the analyte is a DNA or RNA molecule 1004 and each gRNA is complementary to a different nucleic acid sequence within the DNA or RNA molecule 1004. Accordingly, when the DNA or RNA analyte 1004 contacts the sensor, the DNA or RNA analyte 1004 will serve as an activating nucleic acid for RNP complexes including each of guide 11001, guide 21002, and guide 31004. Binding of the gRNAs by the DNA analyte will produce active RNP complexes including each of guides 1, 2, and 3 which will cleave (e.g., non-specifically or specifically) a linker to release the reporter and produce a detectable signal (e.g., a color change due to a change in a structural property of the sensor) indicative of the presence of the analyte (not shown in FIGURE 10). Activation of RNP complexes including multiple, different gRNAs allows for amplification of the detectable signal. [0117] Analytes may be detected and/or quantified in a variety of samples. The sample can be in any form that allows for measurement of the analyte. In certain embodiments, the sample is a body fluid sample, such as a blood, serum, plasma, urine, cerebrospinal fluid, or interstitial fluid sample. [0118] Analytes include biological molecules, for example, a protein, peptide, carbohydrate, glycoprotein, glycopeptide, lipid, lipoprotein, nucleic acid, or nucleoprotein. Exemplary analytes include, for example, cells, antibodies, antigens, virus particles, pathogenic bacteria, ions, spores, yeasts, molds, cellular metabolites, enzymes, enzyme inhibitors, receptor ligands, peptides, proteins, fatty acids, steroids, hormones, enzymes, and nucleic acids. Other non- biological analytes that can be detected can include, for example, organic compounds, synthetic molecules, metals, ions, metal complexes, drugs, nerve agents, and narcotic agents. Exemplary Sensor Embodiments [0119] In some embodiments, the reporters described above are bound to a sensor surface by a nucleic acid (e.g., DNA) linker. Cleavage of the nucleic acid (e.g., DNA) linker results in a structural destruction of the reporter system, thereby causing an observable property change in the sensor. The observable property change may result from, for example, a surface energy change in a portion of the sensor, a wetting behavior change, or another physical property change (e.g., destruction of at least a portion of a structural color indicator). As a result of the property change, a portion of the sensor may change color or may suffer a color degradation or there may be a change in (or loss of) a monitored electrical signal, an optical signal, or the like. In general, any sensor that undergoes any observable property change as a result of reporter system destruction is within the scope of the invention. Several exemplary embodiments of such sensors are described below. [0120] FIGURES 11A and 11B depict one embodiment of a surface property sensor (or indicator) 1100. As illustrated, a surface 1101 of the sensor 1100 is bound to a hydrophobic moiety 1102 by a nucleic acid (e.g., DNA) linker 1103. Accordingly, as depicted in FIGURE 11A, the surface 1101 of the sensor 1100 is initially hydrophobic. As illustrated in FIGURE 11B, cleavage of the nucleic acid (e.g., DNA) linker 1103 by an RNP complex 1104 (see FIGURE 11A) releases the hydrophobic moiety 1102, thereby rendering the surface 1101 of the sensor 1100 more hydrophilic. A hydrophobic to hydrophilic transition may be visualized by observing the transition from, e.g., fluid rolling off or beading on the surface 1101 to spreading out on the surface 1101. In certain embodiments, to enhance the hydrophobicity of the surface 1101, the surface 1101 may be rough. A rough surface may be, for example, a surface with a roughness parameter, such as arithmetic average roughness, of greater than 0.001 nm. The surface 1101 may be rendered rough by the inclusion thereon of, for example, a micropillar or nanopillar array (e.g., either a periodic array or an aperiodic array). [0121] FIGURES 12A and 12B depict one embodiment of a structural color sensor (or indicator) 1200, in particular a surface plasmon resonance-type colorimetric sensor 1200. As illustrated, the sensor 1200 includes a plasmonic array of nanopillars (or, alternatively, micropillars) 1204. Each nanopillar 1204 may be manufactured of a dielectric or insulative material (e.g., silica, titanium dioxide, silicon nitride, and the like). A first layer of metal 1208 may be deposited on the upper surface of a substrate 1212 and a second layer of metal 1210 may be deposited on the upper surface of each of the nanopillars 1204. The metal for the layers 1208, 1210 may be, for example, platinum, gold, silver, aluminum, copper, tungsten, and combinations thereof, and the layers 1208, 1210 may be relatively thin (e.g., each layer 1208, 1210 may be 0.1 nm to several hundreds of nanometers thick). Each nanopillar 1204 is separated from another, adjacent nanopillar 1204 by a gap 1216, which can be tuned, for example, from one (1) nm to one (1) mm. These narrow gaps 1216 can form deep interconnected sensing channels. As further illustrated, a surface grafted DNA brush 1220 with a hydrophobic moiety 1224 is bound to the metal layer 1210 deposited on the top of each nanopillar 1204. Accordingly, as depicted in FIGURE 12A, the top surface of the nanopillars 1204 are initially hydrophobic. As illustrated in FIGURE 12B, cleavage of the DNA linker 1220 by an RNP complex 1228 (see, FIGURE 12A) releases the hydrophobic moiety 1224, thereby rendering the top surface of the nanopillars 1204 hydrophilic. [0122] FIGURES 13A and 13B demonstrate how the sensor 1200 operates to detect a fluid containing a target analyte of interest. With reference to FIGURE 13A, when the sensor surface is initially hydrophobic, a fluid 1304 that does not include a target analyte of interest is not able to penetrate the gaps 1216 between the nanopillars 1204 (i.e., a Cassie-Baxter wetting mode may be observed). In contrast, with reference to FIGURE 13B, when a fluid 1308 that contains the target analyte of interest is present, the RNP complex 1228 (see FIGURE 12A) cleaves the DNA linkers 1220 via a non-specific (or specific) cleavage of the phosphodiester (or other) bond on those DNA linkers 1224, thereby releasing the hydrophobic moiety 1224 from the sensor surface and causing the top surface of the nanopillars 1204 to become hydrophilic and inducing a surface energy change. As a result, as illustrated in FIGURE 13B, the fluid 1308 penetrates into the gaps 1216 between the nanopillars 1204 (i.e., a Wenzel wetting mode may be observed), which leads to a color change in the sensor 1200. [0123] In some implementations, and with reference again to FIGURES 12A and 12B, the structural color is generated from a plasmonic color effect due to the strong coupling between the metal 1210 on the top surfaces of the nanopillars 1204 and the thin film of metal 1208 deposited on the upper surface of the substrate 1212 (e.g., underneath the array of nanopillars 1204). In operation, the effective refractive index in the localized environment of the structural color sensor 1200 changes due to the infiltration of the fluid into the gaps 1216 between the nanopillars 1204. In many cases, this change in the effective refractive index affects the dipole interaction between the metallic surfaces 1208, 1210 deposited on the upper surface of the substrate 1212 and on the upper surface of each of the nanopillars 1204. This dipole interaction determines the scattered hybridized plasmon resonance, i.e., the color. Accordingly, as an example, the surface grafted DNA brush 1220 with the hydrophobic moiety 1224 may make the plasmonic array of nanopillars 1204 exhibit a first color (e.g., blue) by keeping a fluid out of the gaps 1216 between the nanopillars 1204 due to the hydrophobic effect. When, however, the fluid is allowed to penetrate the gaps 1216 following the cleavage of the hydrophobic moiety 1224, a color different from the initial color (e.g., red) may be produced. In one embodiment, the DNA brush 1220 is thick enough to shift the plasmonic resonance of the array of nanopillars 1204 so that a cleaving event by the RNP complex 1228 induces a direct color change. In another embodiment, a thick polymer brush may be grafted to the DNA brush 1220 to increase the thickness so that a cleaving event by the RNP complex 1228 induces a direct color change with higher contrast. [0124] Referring now to the flow chart depicted in FIGURE 14, one exemplary method of producing the surface plasmon resonance-type colorimetric sensor 1200 depicted in FIGURES 12A–12B and 13A–13B is shown. After providing a base substrate 1212 (STEP 1) and applying a photoresist layer (STEP 2), a nanopattern with predetermined geometry can be generated and transferred to the photoresist layer via electron-beam lithography (EBL) and an etching process (STEPS 3 and 4). Nanopillars 1204 may be formed after etching part of the photoresist layer or etching into the base substrate 1212. In a next step, a thin layer (e.g., of about 0.1 nm to several hundred nanometers) of metal (e.g., platinum, gold, silver, aluminium, copper, tungsten, combinations thereof, and the like) may be applied (STEP 5) (e.g., by metal deposition, chemical vapor deposition (CVD), sputtering, three-dimensional nanoprinting, plasma-enhanced chemical vapor deposition (PECVD), physical vapor deposition (PVD), electroless plating, and so forth) to the top surfaces of the nanopillars 1204, as well as to the top surface of the base substrate 1212. The top surface of the array of nanopillars 1204 may then be rendered hydrophobic (STEP 6). In particular, a monolayer of ssDNA may be immobilized on the top surface of the metal layer 1210 and a hydrophobic moiety 1224 may be introduced after partially silanizing the DNA molecule. In some implementations, a complementary DNA with hydrophobic moiety 1224 may be hybridized with the surface immobilized strand. The hydrophobic moiety 1224 may be a long chain molecule (e.g., alkane chain molecule) or a molecule bearing such a long alkane chain conjugated with an ssDNA, or it may be another ssDNA with a fluorine modified base, or conjugated with a lipid molecule such as cholesterol. One of ordinary skill in the art will appreciate that other techniques may be used to create the surface plasmon resonance-type colorimetric sensor 1200 without departing from the scope of the present disclosure. One of ordinary skill in the art will also appreciate that the nanopillars 1204 shown in FIGURES 12A– 12B and 13A–13B are only used as a non-limiting examples of a surface nano- or microstructure for structural color generation. Other non-limiting examples include nanohole or microhole arrays or a combination of hole arrays and pillar arrays. [0125] FIGURES 15A and 15B depict another embodiment of a structural color sensor (or indicator) 1500, in particular a surface plasmon resonance-type colorimetric sensor 1500. The structure of the sensor 1500 is similar in some aspects to the sensor 1200 shown in FIGURES 12A and 12B. For example, like the sensor 1200, the sensor 1500 includes a first layer of metal 1508 (e.g., platinum, gold, silver, aluminum, copper, tungsten, and combinations thereof) deposited on an upper surface of a substrate 1512. However, instead of an array of nanopillars 1204 having a metal layer 1210 on a top surface of each nanopillar 1204 (as shown in FIGURES 12A and 12B), the sensor 1500 includes an array of DNA linkers 1504 conjugated with a metal (or sometimes latex or other type of) nanoparticle 1510. Non-limiting examples of such nanoparticles 1510 include gold nanoparticles, polystyrene nanoparticles, CdSe quantum dots, carbon nanoparticles, or combinations of these nanoparticles, or conjugates of these nanoparticles with dye/pigment. [0126] To facilitate description, a metal nanoparticle 1510 is used as a non-limiting example. In such a case, the structural color exhibited by the sensor 1500 depicted in FIG.15A is generated from the interaction of the metal nanoparticles 1510 with the thin film of metal 1508 underneath the patterned DNA linkers 1504 (e.g., in the same fashion that the structural color exhibited by the sensor 1200 depicted in FIGURES 12A and 12B is generated from the interaction of the metal layers 1208, 1210). More particularly, the scattered, reflected, or transmitted color is determined, e.g., primarily or at least in part, by a localized plasmon resonance between the two metal surfaces 1508, 1510 that are separated by a coupling distance (e.g., by the height of each DNA linker 1504). According to the Mie theory, the size and shape of the metal surfaces 1508, 1510 affect the plasmon resonance. Periodicity between adjacent metal surfaces (e.g., between top surfaces of adjacent DNA linkers 1504, where the nanoparticles 1510 are located) also affects the plasmon resonance. For example, the closer the metallic surface 1508 is to the metallic surfaces 1510, the greater the coupling between the interacting dipoles of the two metallic surfaces 1508, 1510. The greater the interactive dipole coupling, the greater the increase of the plasmon resonant wavelength. In contrast, the more distant the metallic surfaces 1508, 1510 are from one another, the weaker the coupling between the interacting dipoles, resulting in a decrease of the plasmon resonant wavelength. Moreover, the structural color generated by the sensor 1500 depicted in FIGURE 15A may either be the extinction (small metal particles) or scattering (large metal particles) from individual particles (e.g., Mie extinction or scattering), where “small” indicates a size range of the metal nanoparticles 1510 from 0.001 nm to 30 nm and large indicates a size range of the metal nanoparticles 1510 from 30 nm to 2 micrometers. [0127] As illustrated in FIGURE 15B, when a fluid sample containing a target analyte of interest is introduced to the sensor 1500 and the RNP complex 1528 (see FIGURE 15A) is activated by an activating nucleic acid sequence, the RNP complex 1528 may non-specifically (or specifically) cleave the DNA linkers 1504, thereby decoupling a top portion of the DNA linker 1504 (including the conjugated metal nanoparticle 1510) from the remaining portion of the sensor 1500 (including the first layer of metal 1508). The decoupling of the metal nanoparticle 1510 from the first metal layer 1508 results in a degradation of the color exhibited by the sensor 1500 (e.g., a return from a first color exhibited by the sensor 1500 prior to the decoupling to the color of the first layer of metal 1508), thereby indicating the presence of the target analyte of interest in the fluid sample. [0128] In one exemplary method of manufacturing the surface plasmon resonance-type colorimetric sensor 1500, a thin layer (e.g., of about 0.1 nm to several hundred nanometers) of metal 1508 (e.g., platinum, gold, silver, aluminium, copper, tungsten, combinations thereof, and the like) may be applied to a top surface of the base substrate 1512 (e.g., by metal deposition, chemical vapor deposition (CVD), sputtering, three-dimensional nanoprinting, plasma-enhanced chemical vapor deposition (PECVD), physical vapor deposition (PVD), electroless plating, and so forth). An array of DNA linkers 1504 may then be produced from, e.g., a surface-initiated polymerization (SIP) or surface-initiated hybridization chain reaction. Metal nanoparticles 1510 conjugated with complementary ssDNA may be grafted to the array of DNA pillars 1504. In some implementations, the initial patterned surface may be made from a variety of processes, including but not limited to electron beam chemical lithography (EBCL), soft lithography, surface initiated ATRP and RAFT polymerization. In some implementations, DNA molecules may be co-polymerized or functionalized with polymer brushes via click chemistry reaction. For a non-limiting example, polymer brushes with amine pendant groups (or other groups) may be employed for a reaction with a carboxylic acid group (or other group) on the biotin modified DNA molecules. [0129] FIGURES 16A and 16B depict yet another embodiment of a structural color sensor (or indicator) 1600, in particular a surface plasmon resonance-type colorimetric sensor 1600. The structure of the sensor 1600 is similar in some aspects to the sensor 1200 shown in FIGURES 12A and 12B. For example, like the sensor 1200, the sensor 1600 includes array of nanopillars 1604. Each nanopillar 1604 may be manufactured of a dielectric or insulative material (e.g., silica, titanium dioxide, silicon nitride, and the like). Also in a similar fashion to the sensor 1200, a first layer of metal 1608 may be deposited on the upper surface of a substrate 1612 and a second layer of metal 1610 may be deposited on the upper surface of each of the nanopillars 1604. The metal for the layers 1608, 1610 may be, for example, platinum, gold, silver, aluminum, copper, tungsten, and combinations thereof, and the layers 1608, 1610 may be relatively thin (e.g., each layer 1608, 1610 may be 0.1 nm to several hundreds of nanometers thick). However, in the sensor 1600 depicted in FIGURE 16A, the second layer of metal 1610 may be much thinner than the first layer of metal 1608. The nanopillars 1604, substrate 1612, and first and second metal layers 1608, 1610 may be manufactured, for example, as described above with reference to Steps 1–5 of FIGURE 14. The very thin (e.g., 5 nm) second layer of metal 1610 provides a support for immobilization of DNA linkers 1620, which may be used as the anchor to hybridize with a complementary strand conjugated with a metal (or sometimes latex or other type of) nanoparticle 1624. [0130] To facilitate description, a metal nanoparticle 1624 is used as a non-limiting example. In such a case, the coupling between the metal nanoparticle 1624 and the first layer of metal 1608 underneath the nanopillars 1604 generates the visible structural color (i.e., plasmonic color) previously described. As illustrated in FIGURE 16B, when a fluid sample containing a target analyte of interest is introduced to the sensor 1600 and the RNP complex 1628 (see FIGURE 16A) is activated by an activating nucleic acid sequence, the RNP complex 1628 may cleave the DNA linker 1620 coupled to the metal nanoparticles 1624. As a result, the color generated by the sensor 1600 may be degraded due to a decoupling of the plasmonic interaction when the metal nanoparticles 1624 are released from the remainder of the sensor 1600, which indicates the presence of the target analyte of interest in the fluid sample. For example, there may be a return from a first color exhibited by the sensor 1600 prior to the decoupling to the color of the first layer of metal 1608. [0131] The sensors (or indicators) 1100, 1200, 1500, and 1600 described above with reference to FIGURES 11A–11B, 12A–12B, 15A–15B, and 16A–16B, respectively, have all been described in the context of the sensor (or indicator) 1100, 1200, 1500, 1600 being located (e.g., on a pad) separate from the CRISPR pad containing the RNP complex, such as shown in FIGURE 1. Alternatively, as shown in FIGURE 2, a sensor (or indicator) may be located on the same pad as the RNP complex. [0132] FIGURE 17 illustrates an embodiment where a pad 1702 comprises both a sensor (or indicator) 1700 and an RNP complex 1728. In particular, the pad 1702 may be an enclosed cavity or a flow-through microfluidic device having a top surface 1706 and a bottom surface 1712. As shown, the RNP complex 1728 may be physically or chemically immobilized on the inner top surface 1706 of the pad 1702, while DNA molecules 1720 having hydrophobic moieties 1724 may be functionalized on an array of nanopillars (or micropillars) 1704 fixed on the inner bottom surface 1712 of the pad 1702. Each nanopillar 1704 may be manufactured of a dielectric or insulative material (e.g., silica, titanium dioxide, silicon nitride, and the like). In addition, a signal indicator may be located on the inner bottom surface 1712 of the pad 1702 underneath the nanopillars 1704. The signal indicator may be colorimetric or any other type of signal indicator. As a non-limiting example, the colorimetric indicator may be a metal-dielectric stack that generates a structural color from light-matter interaction. More specifically, a layer of metal 1708 (e.g., platinum, gold, silver, aluminum, copper, tungsten, and combinations thereof) may be deposited on the inner bottom surface 1712 of the pad 1702 and a dielectric (e.g., an oxide) 1707 may be deposited on top of the metal 1708. In such a fashion, the metal-dielectric stack generates (in the absence of a fluid thereon) a first (e.g., blue) structural color from the light-matter interaction. In the presence of a fluid (e.g., when a fluid penetrates the gaps 1716 between the nanopillars (or micropillars) 1704 and makes contact with the metal-dielectric stack), the effective refractive index in the localized environment of the metal-dielectric stack changes, such that the metal-dielectric stack generates a second, different (e.g., red) structural color from the light-matter interaction. Alternatively, the signal indicator located on the inner bottom surface 1712 of the pad 1702 underneath the nanopillars 1704 may be any other indicator that will exhibit an observable change upon contact with a fluid. Other exemplary colorimetric indicators that could be employed as the signal indicator include nanoparticles, Bragg reflective coatings, photonic crystals, interference based thin film reflectors, plasmonic arrays of micropillars or nanopillars, plasmonic nanoparticle thin films, dyes and pigments, hydrochromic inks, and materials coated with hydrochromic ink. [0133] In one embodiment, the hydrophobic moieties 1724 maintain a Cassie-Baxter state (e.g., as previously described with reference to FIGURE 13A) so that a fluid sample lacking a target analyte of interest is prevented from penetrating into the gaps 1716 between the nanopillars (or micropillars) 1704. Once, however, the RNP complex 1728 is activated by an activating nucleic acid sequence (i.e., once a fluid sample containing a target analyte of interest is introduced to the sensor 1700), the RNP complex 1728 cleaves the DNA linkers 1720, such that the hydrophobic moieties 1724 are removed from the sensor 1700. This enables a wetting state transition from the first state (e.g., the Cassie-Baxter state) to a second state (e.g., a Wenzel state, as previously described with reference to FIGURE 13B), thereby allowing the fluid sample to penetrate into the gaps 1716 between the nanopillars 1704 and to come into contact with the signal indicator underneath the nanopillars 1704. Where the signal indicator is colorimetric, a change in color therefore occurs, which indicates the presence of the target analyte of interest in the fluid sample. [0134] FIGURES 18A and 18B depict an embodiment of a sensor (or indicator) 1800 where an electrical readout signal can be generated. As illustrated, the sensor 1800 includes an electrode 1804 (manufactured from, for example, gold), a polymer brush 1808, DNA linkers 1812, and a redox tag 1816. In some implementations, the polymer brush 1808 may be grafted from a surface of the electrode 1804 to improve the signal-to-noise ratio of the electrical readout. A conducting polymer or electrochromic materials may be used in place of the polymer brush 1808 or be co-polymerized or physically blended with the polymer brush 1808. Non-limiting examples include polypyrrole (PPy), polyaniline (PANI), Poly(3,4-ethylenedioxythiophene) (PEDOT), or tungsten oxide (WO₃). The redox tag 1816 (e.g., methylene blue or ferrocene) may be tagged to the DNA linker 1812 and immobilized to the polymer brush 1808 surface or sometimes directly immobilized on the electrode 1804 surface. [0135] In operation, the electrical current passing through the electrode 1804 is measured. The amount of electrical current measured depends, in part, on the proximity of the redox tag 1816 to the electrode 1804. As illustrated in FIGURE 18B, when a fluid sample containing a target analyte of interest is introduced to the sensor 1800 and the RNP complex 1828 (see, FIGURE 18A) is activated by an activating nucleic acid sequence, the RNP complex 1828 may cleave the DNA linkers 1812 attached to the redox tags 1816. Accordingly, the redox tags 1816 are released from the remainder of the sensor 1800 and move away from the electrode 1804, resulting in a change (e.g., a reduction) in the amount of electrical current measured to be passing through the electrode 1804 due to the change in the redox chemical reaction. This change in electrical current is indicative of the presence of the target analyte of interest in the fluid sample. In various embodiments, the change in electrical current may result in (e.g., an audible or visual) alarm being provided to a user of the sensor 1800 (e.g., should the current change be greater than a threshold current change). [0136] FIGURES 19A and 19B depict an embodiment of a sensor (or indicator) 1900 where an optical readout employing a Raman signal can be generated. As illustrated, the sensor 1900 includes Raman reporter molecule tags 1904 (e.g., Rhodamine 6G or 4-mercaptopyridine), each of which is pre-loaded in a metal nanoparticle 1908. Each metal nanoparticle 1908 may be covalently linked to a DNA linker 1912 that is immobilized on a Raman active surface 1918, such as, for example, a metal thin film with isolated metal islands. [0137] As one non-limiting example, surface-enhanced Raman scattering (SERS) is a spectroscopic method that may be used in chemical and/or biological sensing for the purpose of detecting the presence or absence of individual molecules, e.g., the Raman reporter molecule tags 1904. More specifically, Raman scattering, using a spectrometer capable of detecting a molecular vibrational spectrum, is predicated on the notion that any Raman reporter molecule tag 1904 that is employed will have a unique Raman scattering spectrum, displaying, upon illumination (e.g., by a laser light-emitting device), discrete, specific (Raman) peaks that can be collected and used to identify or confirm the presence of the Raman reporter molecule tag 1904 with a high degree of accuracy. [0138] Accordingly, in operation, a high intensity laser light source is directed towards the sensor 1900 and a Raman spectrometer is employed to generate a Raman scattering spectrum. Where the Raman reporter molecules 1904 are present in the sensor 1900, a distinct Raman scattering spectrum identifying the presence of the Raman reporter molecules 1904 is generated. However, as illustrated in FIGURE 19B, when a fluid sample containing a target analyte of interest is introduced to the sensor 1900 and the RNP complex 1928 is activated by an activating nucleic acid sequence, the RNP complex 1928 may cleave the DNA linkers 1912 that are attached to the Raman reporter molecules 1904 pre-loaded in the metal nanoparticles 1908. Accordingly, the Raman reporter molecules 1904 are released from the remainder of the sensor 1900 and move away from the area of the sensor 1900 being interrogated by the Raman spectrometer, resulting in a change in the Raman scattering spectrum generated by the Raman spectrometer. This change in the Raman scattering spectrum is indicative of the presence of the target analyte of interest in the fluid sample. [0139] As another non-limiting example, the fluorescence emission from a fluorophore tag molecule may be monitored. For example, the intensity of the fluorescence (either from the sensor surface or from the fluid that is in contact with the sensor surface) may be monitored by using a spectrophotometer. Incorporation by Reference [0140] The entire disclosures of each of the patent documents and scientific articles cited herein are incorporated by reference herein in their entirety for all purposes. Equivalents [0141] The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein. [0142] What is claimed is:

Claims

CLAIMS 1. A sensor for detecting an analyte of interest in a sample, the sensor comprising: (a) a surface associated with a ribonucleoprotein (RNP) complex comprising: (i) a CRISPR associated (Cas) nuclease; and (ii) a guide RNA (gRNA) comprising a region that binds to the Cas nuclease, and a region that is complementary to an activating nucleic acid sequence; and (b) a surface associated with a reporter that is tethered to the surface by a nucleic acid linker comprising a target nucleic acid sequence; wherein the sensor is configured such that, when the analyte contacts the sensor, the guide RNA binds to the activating nucleic acid, and the RNP complex cleaves the target nucleic acid sequence, thereby releasing the reporter and producing a detectable signal indicative of the presence of the analyte.

2. The sensor of claim 1, wherein the reporter is part of an indicator and release of the reporter destroys at least a portion of a physical structure of the indicator.

3. The sensor of claim 2, wherein the indicator comprises a structural color indicator.

4. The sensor of any one of claims 1-3, wherein the release of the reporter causes a change in a surface property of the surface associated with the reporter.

5. The sensor of claim 4, wherein the surface associated with the reporter changes from hydrophobic to hydrophilic.

6. The sensor of any one of claims 1-5, wherein the nucleic acid linker is covalently bound to the surface.

7. The sensor of any one of claims 1-6, wherein the activating nucleic acid is single- stranded DNA (ssDNA), double-stranded DNA (dsDNA), or RNA.

8. The sensor of any one of claims 1-7, wherein the target nucleic acid is single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), or RNA.

9. The sensor of any one of claims 1-8, wherein the Cas nuclease is a type V Cas nuclease.

10. The sensor of claim 9, wherein the type V Cas nuclease is Cas12a (Cpf1), Cas12b (C2c1), Cas12d, Cas12f (Cas14), or Cas12g.

11. The sensor of any one of claims 1-10, wherein the Cas nuclease is a type VI Cas nuclease.

12. The sensor of claim 11, wherein the type VI Cas nuclease is Cas13a (C2c2), Cas13b, or Cas13d.

13. The sensor of any one of claims 1-12, wherein the analyte is a nucleic acid comprising the activating nucleic acid sequence.

14. The sensor of any one of claims 1-13, wherein the sensor further comprises: (c) a surface associated with an analyte-binding agent that binds to the analyte.

15. The sensor of claim 14, wherein upon binding of the analyte to the analyte-binding agent, the activating nucleic acid sequence is exposed for binding to the gRNA.

16. The sensor of claim 14 or 15, wherein analyte-binding agent comprises the activating nucleic acid sequence.

17. The sensor any one of claims 14-16, wherein the sensor further comprises: (d) a surface associated with a nucleic acid comprising the activating nucleic acid sequence.

18. The sensor of any one of claims 1-17, wherein the surface associated with the RNP complex and the surface associated with the reporter are the same surface.

19. The sensor of any one of claims 1-17, wherein the surface associated with the RNP complex and the surface associated with the reporter are different surfaces.

20. The sensor of claim 18, wherein the surface associated with the RNP complex and the surface associated with the reporter are spaced apart from one another.

21. The sensor of any one of claims 14-17, wherein the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the analyte- binding agent are the same surface.

22. The sensor of any one of claims 14-17, wherein the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the analyte- binding agent are different surfaces.

23. The sensor of claim 22, wherein the surface associated with the RNP complex, the surface associated with the reporter, and the surface associated with the analyte-binding agent are spaced apart from one another.

24. The sensor of any one of claims 14-23, wherein the analyte binding agent is an aptamer or riboswitch.

25. The sensor of claim 24, wherein the analyte binding agent is an aptamer.

26. The sensor of any one of claims 1-25, wherein the RNP complex is tethered to the surface by a nucleic acid linker.

27. The sensor of claim 26, wherein the nucleic acid linker comprises the target nucleic acid sequence.

28. The sensor of claim 27, wherein the nucleic acid linker is covalently bound to the surface.

29. The sensor of any one of claims 1-28, wherein the RNP complex is disposed within a hydrogel that is associated with the surface.

30. The sensor of any one of claims 1-29, wherein the reporter comprises a hydrophobic moiety.

31. The sensor of claim 30, wherein release of the hydrophobic moiety produces a visually detectable change.

32. The sensor of claim 30 or 31, wherein release of the hydrophobic moiety produces a detectable surface property change.

33. The sensor of claim 30 or 31, wherein release of the hydrophobic moiety produces a detectable color change.

34. The sensor of any one of claims 1-33, wherein the reporter comprises a nanoparticle.

35. The sensor of claim 34, wherein release of the nanoparticle produces a detectable color change.

36. The sensor of any one of claims 1-35, wherein the reporter comprises a redox tag.

37. The sensor of any one of claims 1-36, wherein the reporter comprises a Raman tag.

38. The sensor of any one of claims 1-37, wherein the reporter comprises a fluorophore.

39. The sensor of any one of claims 1-38, wherein the sample is a fluid sample.

40. The sensor of any one of claims 1-39, wherein the sensor is disposed upon or integrated within a surface of a fluid receptacle or a straw.

41. The sensor of any one of claims 1-40, wherein the analyte is selected from a metal ion, a small molecule, a protein, or a nucleic acid.

42. The sensor of any one of claims 1-41, wherein the analyte is selected from a narcotic drug, an opioid, a date rape drug, lead (Pb) ions, a biomarker, an allergen, an aflatoxin, and a viral, fungal, or bacterial nucleic acid sequence.

43. The sensor of any one of claims 1-42, wherein the sensor comprises two or more different RNP complexes comprising two or more different gRNAs.

44. A sensor for detecting an analyte of interest in a sample, the sensor comprising a surface associated with a reporter that is tethered to the surface by a nucleic acid linker comprising a target nucleic acid sequence, wherein the sensor is configured such that, when the surface is contacted with (a) the analyte, and (b) a ribonucleoprotein (RNP) complex comprising (i) a CRISPR associated (Cas) nuclease; and (ii) a guide RNA (gRNA) comprising a region that binds to the Cas nuclease, and a region that is complementary to an activating nucleic acid sequence, the guide RNA binds to the activating nucleic acid, and the RNP complex cleaves the target nucleic acid sequence, thereby releasing the reporter and producing a detectable signal indicative of the presence of the analyte.

45. A method for detecting an analyte of interest in a sample, the method comprising contacting the sensor of any one of claims 1-44 with the sample, and detecting a detectable signal resulting from cleavage of the target nucleic acid sequence by the RNP complex.

46. A method for detecting an analyte of interest in a sample, the method comprising contacting a sensor comprising a surface associated with a reporter that is tethered to the surface by a nucleic acid linker comprising a target nucleic acid sequence with (a) the sample, and (b) a ribonucleoprotein (RNP) complex comprising (i) a CRISPR associated (Cas) nuclease; and (ii) a guide RNA (gRNA) comprising a region that binds to the Cas nuclease, and a region that is complementary to an activating nucleic acid sequence, such that the guide RNA binds to the activating nucleic acid, and the RNP complex cleaves the target nucleic acid sequence, thereby releasing the reporter and producing a detectable signal indicative of the presence of the analyte.