Analyte detection system and method

Abstract

The present invention relates to an analyte detection system and method, the system comprising: one or more LC circuits, each with a capacitor and a flat coil; at least one receiver arranged on the coils of the LC circuits and configured to interact with a specific analyte, forming a recognition complex; and at least one detection device connected to the LC circuits and configured to determine variations in the resonance frequency of the LC circuits when the recognition complex is formed, thereby indicating the presence of the analyte as a result of a variation of the inter-winding stray capacitance of the coil causing the modification of the dielectric path between windings. The system can be used as a stand-alone system, in a test strip or in a lateral flow strip.

Description

[0001] ANALYTE DETECTION SYSTEM AND METHOD

[0002] OBJECT OF THE INVENTION

[0003] The present invention falls within the area of ​​analyte detection systems, more particularly, pathogen detection systems.

[0004] The invention relates to an analyte detection system that uses an LC circuit for sensing. The system of the invention can be applied in gases and liquids.

[0005] BACKGROUND OF THE INVENTION

[0006] Label-free biosensors are typically classified by transducer type into reagent-based and reagent-free platforms.

[0007] Traditional reagent-free and label-free platforms include optical (such as SPR), optical interference spectroscopy, gravimetry (e.g., quartz crystal microbalance QCM), and electrochemistry. The high cost of reagent-free and label-free biosensors based on SPR and QCM prevents their widespread use.

[0008] RLC circuits are generally used to create frequency filters or impedance transformers. This sensor consists of an inductor, a resistor, and a capacitor, and can involve multiple inductors and capacitors, thus becoming known as LC networks. Since the resonant frequency of the RLC circuit is sensitive to the surrounding environment due to the dependence of the inductance value on the magnetic permeability of the medium, they are also used as non-contact proximity sensors. The closer the target is to the circuit, the greater the impact on the magnitude and frequency of the oscillation. The detection range of an RLC sensor depends on the type of material that alters the inductor's magnetic field. Ferrous metals, such as iron and steel, allow for a greater detection range, while non-ferrous metals, such as aluminum and copper, can reduce the detection range by up to 60%.Among the most common applications for RLC sensors are metal detectors, traffic lights, car washes, and a variety of automated industrial processes. Since the sensor requires no physical contact, it is especially useful in hard-to-reach applications.

[0009] State-of-the-art RLC sensors in solution have also been developed that detect changes in magnetic fields (magnetic permeability) due to the presence of magnetic particles.

[0010] However, no solution has been found in the state of the art that allows organic systems not bound to magnetic particles to be detected with LC sensors at a low cost and with high robustness.

[0011] DESCRIPTION OF THE INVENTION

[0012] The invention relates to an analyte detection system that allows detection by means of an LC circuit.

[0013] The detection system relies on changes in electrical permittivity in the vicinity of an LC circuit inductor, due to the formation of a recognition complex between the analyte and a receptor on the inductor's surface. The formation of these complexes modifies the inductor's parasitic capacitances and, consequently, the LC circuit's resonant frequency. However, the formation of the recognition complex does not produce changes in the inductor's magnetic field, as the recognition complex has no relevant magnetic properties.

[0014] The system of the invention makes use of the parasitic capabilities of the inductors to accurately detect analytes. These analytes are specifically recognized by receptors attached to the inductor surface of the LC circuits.

[0015] The proposed transducer detection mechanism is based on the use of the inter-turn parasitic capacitances of the inductor in LC circuits (inductance-capacitor), i.e., the modification of the dielectric constant of the medium, for the detection and monitoring of analytes such as bacteria, viruses, and other chemical species. Thus, the invention relates to an analyte detection system comprising one or more LC circuits. The LC circuits, in turn, comprise a flat coil and a capacitor.

[0016] Preferably, the equivalent circuit of a planar inductor includes not only the pure inductance value (LS) but also some other parasitic components such as series resistance (RS) and inter-turn capacitance (CS).

[0017] The system of the invention further comprises at least one receptor arranged on the flat coil of the LC circuit and configured to interact with a specific analyte, forming a recognition complex.

[0018] The system of the invention also comprises at least one detection device connected to the LC circuits. The detection device is configured to determine variations in the resonant frequency of the LC circuits. These variations in the resonant frequency occur when the recognition complex is formed, due to the modification of the dielectric path between turns, which produces a variation in the parasitic inter-turn capacitance of the coil, such that they serve to determine the presence of the analyte.

[0019] In a first embodiment, the detection system of the invention can be used as an environmental detector, such that the LC circuitry with the receivers are located on a support and in contact with the environment.

[0020] Alternatively, the system of the invention may also comprise a test strip made of porous material, which will act as a support.

[0021] In this case, the analyte detection system of the invention comprises:

[0022] - one or more LC circuits comprising: a flat coil and a capacitor;

[0023] - at least one receptor configured to interact with a specific analyte, forming a recognition complex;

[0024] - a test strip made of porous material, comprising: a first side on which the LC circuits are arranged, and a second side to which the at least one receptor is adhered; and - at least one detection device connected to the LC circuits and configured to determine variations in the resonant frequency of the LC circuits when the recognition complex is formed, thereby indicating the presence of the analyte.

[0025] The test strip can preferably be made of nitrocellulose or polyethylene terephthalate.

[0026] Alternatively, the system of the invention may further comprise at least one lateral flow strip.

[0027] In this case, the analyte detection system of the invention comprises:

[0028] - one or more LC circuits comprising: a flat coil and a capacitor;

[0029] - at least one receptor configured to interact with a specific analyte, forming a recognition complex;

[0030] - at least one lateral flow strip, comprising: a first face, comprising a receptor region and a capture region, defined by one or more capture lines to which the at least one receptor adheres, and / or a second face, on which the LC circuits are arranged in a position corresponding to the position of the capture lines; and

[0031] - at least one detection device connected to the LC circuits and configured to determine variations in the resonance frequency of the LC circuits upon formation of the recognition complex, thereby indicating the presence of the analyte.

[0032] The lateral flow strip comprises a receptor region and a capture region.

[0033] In this case, the LC circuits are arranged in a test and / or control line of the lateral flow strip and the at least one receptor adheres to the test and / or control line of the lateral flow strip.

[0034] Additionally, the lateral flow strip may further comprise a reservoir region located at an end opposite the strip to the receptor region. In this case, the at least one receptor may be an immobilized detection agent adhered to the test and / or control line of the lateral flow strip.

[0035] More preferably, the system of the invention further comprises a gold or carbon nanoparticle conjugate located on the receptor to amplify variations in the resonant frequency of the LC circuits when the recognition complex is formed.

[0036] Preferably, in the system of the invention, the receiver can form a self-assembled monolayer with the LC circuits.

[0037] The system of the invention may also comprise a wireless communication module that connects the at least one detection device with the LC circuits.

[0038] The present invention also relates to a method of analyte detection comprising the steps of:

[0039] - provide one or more LC circuits, each comprising: a flat coil and a capacitor;

[0040] - having at least one receptor in contact with the LC circuit configured to interact with a specific analyte, forming a recognition complex; and

[0041] - determine variations in the resonant frequency of the LC circuit when the recognition complex is formed by means of a detection device connected to the LC circuit.

[0042] In a second set of embodiments, the method may comprise the steps of:

[0043] - provide one or more LC circuits comprising: a flat coil and a capacitor;

[0044] - provide at least one receptor configured to interact with a specific analyte, forming a recognition complex;

[0045] - provide one or more test strips made of porous material;

[0046] - adhere the LC circuits to a first side of the test strips;

[0047] - arranging the at least one receiver on a second side of the test strip in a position corresponding to the position of the LC circuit;

[0048] - immersing the test strips in a sample fluid to form the recognition complex; and determining variations in the resonant frequency of the LC circuit as the recognition complex is formed using a detection device connected to the LC circuit.

[0049] Furthermore, the method of the invention may also comprise a step of amplifying a signal from the detection device generated by the variation in the resonant frequency of the LC circuit by sandwich format, by immersing the strip in a solution with a labeled receptor.

[0050] Preferably, the method may also implement a step of washing the sample fluid, before immersing the test strips in said sample fluid.

[0051] Alternatively, in a third set of embodiments, the method of the invention may comprise the steps of:

[0052] - provide one or more LC circuits comprising: a flat coil and a capacitor;

[0053] - provide at least one receptor configured to interact with a specific analyte, forming a recognition complex, in contact with the LC circuit;

[0054] - providing one or more lateral flow strips, comprising a first side comprising, in turn, a receiving region and a capture region, defined by one or more capture lines;

[0055] - adhere at least one receptor to the capture lines of the lateral flow strip,

[0056] - adhere the LC circuits to a second face in a position corresponding to the position of the capture lines;

[0057] - depositing a sample fluid onto the receiving region of the lateral flow strips for migration to the capture lines and formation of the recognition complex; and

[0058] - determine variations in the resonant frequency of the LC circuit when the recognition complex is formed by means of a detection device connected to the LC circuit.

[0059] In the context of the invention, the term “pathogen” refers to various bacterial, viral, parasitic, and fungal infectious agents. The resistance of various infectious agents to drugs can also be determined using the present invention. A wide variety of infectious diseases, caused by such agents, can also be detected or determined by the method of the present invention. Representative bacterial infectious agents that can be detected and / or determined by the present invention include, but are not limited to, Escherichia coli, Salmonella, Shigella, Klebsiella, Pseudomonas, Listeria monocytogenes, Mycobacterium tuberculosis , etc. Representative fungal infectious agents that can be detected and / or determined by the present invention include, but are not limited to, Cryptococcus neoformans, Blastomyces dermatitidis, Histoplasma capsulatum, Alternaria, Fusarium spp., etc.Representative viral infectious agents that can be detected and / or determined by the present invention include, but are not limited to, human immunodeficiency virus, human T-cell lymphocytotrophic virus, hepatitis viruses (e.g., hepatitis B virus and hepatitis C virus), Epstein-Barr virus, cytomegalovirus, influenza virus, COVID-19 virus, etc. Representative parasitic agents that can be detected and / or determined by the present invention include, but are not limited to, Plasmodium falciparum, Plasmodium malaria, Plasmodium vivax, Plasmodium ovale, Onchoverva volvulus, Leishmania, etc.

[0060] The present invention may also be useful for the detection and / or determination of drug resistance in infectious agents by determining their resistance. For example, vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, etc.

[0061] In the field of clinical monitoring, the present invention can also be used for the detection and / or determination of genetic diseases by detecting genetic biomarkers. This can be carried out through prenatal or postnatal screening for chromosomal and genetic diseases or genetic diseases. Examples of detectable genetic diseases include, but are not limited to, cystic fibrosis, Down syndrome, heart disease, phenylketonuria, Huntington's disease, autoimmune diseases, etc. It can also be used for the detection and / or determination of cancers, such as tumor suppressor genes or genes involved in DNA amplification, replication, recombination, or repair. Examples of these include, but are not limited to, the BRCA1 gene, the p53 gene, etc.Various aspects of the present invention can be used to identify amplifications, large deletions, as well as point mutations and small deletions / insertions of the above genes in the following common human cancers: leukemia, colon cancer, breast cancer, lung cancer, prostate cancer, etc.

[0062] The present invention can be used in a variety of forensic areas, including, for example, human identification for military personnel and criminal investigation, paternity testing and family relationship analysis, HLA compatibility typing, and contamination detection in blood, sperm, or transplant organs. The present invention may be useful for the detection and / or identification of bioterrorist agents / diseases, for example, anthrax, botulism, plague, etc.

[0063] In the food and feed industry, the present invention has a wide variety of applications. For example, it can be used for the identification and characterization of production organisms such as yeast for the production of beer, wine, cheese, yogurt, bread, etc. Another area of ​​use is in connection with quality control and certification of products and processes (e.g., livestock farming, pasteurization, and meat processing) to detect contaminants. Other uses include the characterization of plants, bulbs, and seeds for breeding purposes, the identification of the presence of specific plant pathogens, and the detection and identification of veterinary infections.

[0064] Another area where the present invention can be used is to detect the presence of plant pathogens and pesticides (or their degradation products), not only in greenhouses, but also in growth chambers, transport containers, or the like.

[0065] In the field of environmental monitoring, the present invention can be used, for example, for the detection, identification, and monitoring of pathogenic microorganisms in natural and artificial ecosystems and microcosms, such as in municipal wastewater treatment systems and water reservoirs, or in contaminated areas undergoing bioremediation and / or on beaches. It is also possible to detect plasmids containing genes capable of metabolizing xenobiotics, monitor genetically modified microorganisms in the environment and in industrial plants, etc.

[0066] The term "receptor," as used herein, refers to a compound consisting of or comprising an inorganic substance, a nucleotide polymer (nucleic acid), or an oligopeptide or polypeptide. The term "nucleic acid," as used herein, refers to a nucleotide polymer (e.g., aptamer, etc.). In some embodiments, nucleic acids are or contain deoxyribonucleic acids (DNA); in some embodiments, nucleic acids are or contain ribonucleic acids (RNA). In some embodiments, nucleic acids include naturally occurring nucleotides (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxy guanosine, and deoxycytidine) or non-naturally occurring nucleotides including, but not limited to, nucleoside analogs (e.g.,, 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, C5-propynylcytidine, C5-propynyluridine), chemically modified bases, biologically modified bases (e.g., molyzed bases), intercalated bases, modified sugars (e.g., 2'-fluoribose, ribose), or modified phosphate groups. In some embodiments, nucleic acids include phosphodiester linkages; or more non-phosphodiester structural linkages such as, for example, phosphorothioates and 5'-N-phosphoramidite linkages. In some embodiments, a nucleic acid is an oligonucleotide in that it is relatively short (e.g., less than about 5000 or fewer nucleotides in length). The term "oligopeptide," as used herein, refers to a chain of between 2 and 20 amino acids linked together by peptide bonds.The term "polypeptide," as used herein, refers to a chain of at most 20 amino acids linked together by peptide bonds. In some embodiments, a polypeptide comprises naturally occurring amino acids; alternatively or additionally, in some embodiments, a polypeptide comprises one or more non-natural amino acids (i.e., compounds that do not occur in nature but can be incorporated into a polypeptide chain; see, for example, the assembly of the artificial oligoamino acid Fmoc-Stp(Boc3)-OH into oligomers of defined sequence for the formulation of tumor-targeted plasmid DNA) and / or analogs of known amino acids, e.g., molecularly imprinted polymers, can alternatively be employed). For example, a polypeptide can be a protein (an antibody, an enzyme, a peptide, etc.).In some embodiments, one or more of the amino acids in a polypeptide may be modified, for example, by the addition of functional groups such as a carbohydrate group, a phosphate group, a crosslinking agent or spacer, a conjugatable functional group, or other modification, etc.

[0067] The term “linked” as used herein refers to two or more entities in physical proximity to one another, either directly or indirectly (e.g., through one or more additional entities serving as a crosslinker), to form a stable structure such that the entities remain linked under prevailing conditions, e.g., physiological and / or airborne conditions. At least one of these entities relates to the LC circuit and at least one relates to the receptor. In some instances, the entities are covalently linked to one another. In other instances, the associated entities are non-covalently linked.In some designs, the associated entities are linked to each other by specific noncovalent interactions (i.e., by interactions between ligands that interact with each other by affinity reactions that discriminate between their complement and other substances present in the context of use, such as, for example, streptavidin / avidin interactions, antibody / antigen interactions, etc.). Alternatively or additionally, other weaker noncovalent interactions may provide sufficient stability for the entities to remain bound to each other (such as, for example, metal coordination, physical adsorption, hydrophobic interactions, TT-TT stacking interactions, hydrogen bonding interactions, Van der Waals interactions, magnetic interactions, electrostatic interactions, dipole-dipole interactions, etc.).

[0068] The system of the invention can be used to detect the presence of any analyte that is indicative of a disorder or condition, such as infectious diseases, pregnancy, microbial infections, cancer, autoimmune disorders, cardiac disorders, allergic disorders, drug abuse, and the like. Analytes that can be detected by the disclosed systems and methods include, but are not limited to, proteins and / or peptides, including ligands and receptors; non-protein molecules, such as carbohydrates, phospholipids, and nucleic acids; small molecules; and other molecules of biological interest. Examples of samples that can be analyzed using the disclosed systems and methods include, but are not limited to, blood, serum, plasma, nasal secretions, sputum, urine, saliva, transdermal swabs, cerebrospinal fluid, and vaginal or urethral secretions. Fecal samples can also be analyzed after appropriate processing.

[0069] Thus, the system and method of the invention allow the detection of analytes in a qualitative and quantitative manner, by determining variations in the resonance frequency of the LC circuits.

[0070] In the system of the invention, it is not necessary to know in advance the natural resonance frequencies of the analytes to be analyzed. Furthermore, the detection principle is based on the formation of a recognition complex and the variation in the resonance frequency of the LC circuit due to said formation.

[0071] DESCRIPTION OF THE DRAWINGS

[0072] To complement the description being made and in order to help better understand the characteristics of the invention, in accordance with a preferred example of practical implementation thereof, a set of drawings is attached as an integral part of said description, in which the following has been represented for illustrative and non-limiting purposes:

[0073] Figure 1.- shows an example of a preferred embodiment of the LC circuit for the direct detection of batehophage M13 in the environment, such that the inducer has been coated with specific anti-M13 antibodies.

[0074] Figure 2 shows a diagram representing the LC circuit signal (resonance frequency, f) whose inductor is coated with anti-M13 antibodies after nebulizing 150 pL of 1x PBS, E. coli, and bacteriophage M13 at different concentrations into a chamber. In this case, the detection limit of the system has been estimated as a blank signal plus 3 times its standard deviation.

[0075] Figure 3.- shows a diagram representing the LC circuit signal (resonance frequency, f) whose inductor is located below the test line of a lateral flow strip, where the test line comprises different concentrations of carbon nanoparticles.

[0076] Figure 4.- shows the LC circuit signal (resonance frequency, f) whose inductor is located below the test line of a lateral flow strip, where the test line comprises different concentrations of gold nanoparticles.

[0077] PREFERRED EMBODIMENT OF THE INVENTION

[0078] The present invention describes an analyte detection system and method. In particular, the method of the invention is explained with reference to three preferred embodiments for analyte detection by means of an LC circuit (1 ). The proposed LC circuit (1 ) consists of a fixed value capacitor (CT) and a planar coil (LT) implemented on a printed circuit board (PCB) as shown in Figure 1 . The equivalent circuit of a planar inductor includes not only the pure inductance value (LS) but also some other parasitic components such as series resistance (RS) and inter-turn capacitance (CS).

[0079] The detection system of the present invention is based on the variation of the inter-turn parasitic capacitance of the inductor. This capacitance depends on the width of the turning traces and the distance and dielectric path between them.

[0080] The resonant frequency of LC circuits (1 ) depends primarily on the capacitor value (CT) and the pure inductance value of the planar inductor (LS). However, it is also affected by parasitic components of planar inductors, including the inter-turn capacitance (CS). Although the inter-turn capacitance (CS) has a small capacitance, under some circumstances a small change in its value can produce a large change in the resonant frequency of the LC circuit (1 ).

[0081] The detection mechanism of the proposed detection system consists of modifying the dielectric path between the turns and measuring the change in the resonant frequency of the LC circuit (1 ).

[0082] In a first preferred embodiment of the invention, analytes present in the environment are inspected. This solution can be implemented in the environmental control systems of smart buildings.

[0083] Accordingly, a device for direct detection of analytes in the environment is proposed in Figure 1. The equipment consists of an LC circuit (1 ) whose inductor is coated with one or more receptors (2) that selectively interact with the desired air analytes. The receptor (2) is connected to the LC circuit (1 ) forming a self-assembled monolayer.

[0084] In this embodiment, the combination of these receptors (2) with the air surrounding the inductor surface leads to a certain dielectric path that produces a certain amount of parasitic capacitance (CS). When the planar inductor is exposed to an atmosphere where the antigen is present, the receptors (2) will recognize the antigen and the dielectric path will be modified producing a change in the parasitic capacitance. Consequently, the resonant frequency of the LC circuit (1 ) shifts, allowing detection of the antigen. Such change provides a specific signal to the interacting analyte.

[0085] The sensor's detection principle is thus based on the changes in dielectric properties, charge distribution, dimension, shape and conductivity that result from the formation of the recognition complex formed on the inductor surface.

[0086] The specificity of the system is determined by the chosen receptor (2) that interacts with the desired analyte.

[0087] The system has been successfully tested using bacteriophage M13, see Figure 2. The designed device is highly versatile and allows for the detection of other airborne pathogens; for example, airborne viruses such as measles, influenza, avian flu, and other bacterial diseases such as tuberculosis. In all cases, detection would be achieved through the use of receptors (2) specific to each desired analyte.

[0088] The characteristics of the designed sensor are: low cost, rapid response, noninvasiveness, and flexibility in sensor design. Furthermore, the sensor's wireless connectivity allows for monitoring remote or hard-to-reach environments (e.g., mines, containers, etc.).

[0089] The present invention provides a system for the detection of analytes in the environment in real time, preferably in closed environments such as hospitals, classrooms, commercial premises and even means of transport, allowing appropriate measures to be taken according to the monitored situation.

[0090] These types of measurements are essential in environments where ventilation, and specifically indoor air quality, are key aspects related to health and comfort.

[0091] The present invention thus solves the problems encountered in the continuous detection of bioaerosols. In a second embodiment of the invention, the system also incorporates test strips (dip strips), which are widely used in the clinical, agricultural, and environmental fields due to their ease of use.

[0092] Test strips consist of one (or several) test zones where reagents are placed which, when they come into contact with the analyte of interest, generate a colored product.

[0093] The test strip is immersed for a few seconds in a liquid sample and the analyte present (or not) in the sample generates (or not) a color change that can be detected visually or with specific equipment that quantifies the optical signal.

[0094] Currently, there are a wide variety of companies that market multi-analyte test strips that allow for semi-quantification of the amount of analyte in the sample using a color chart or quantification using optical instruments.

[0095] The proposal of the invention is to quantify the signal obtained in the test strips by means of LC networks, which are a set of LC circuits (1 ). The system, in this case, consists of an LC network whose inductors are adhered to a porous material, test strips, on which one, or vapors, receptors (2) are joined that selectively interact with the target analyte. The detection principle of the inductive sensor is thus based on the changes in the dielectric properties and conductivity that result from the formation of the recognition complex formed in the test strips. The specificity of this system is given by the specificity of the receptors (2) used in the strip.

[0096] A system is provided for detecting the presence of an analyte, or component, of interest in a sample, preferably a biological sample. The test device comprises a test strip formed from a porous material (such as nitrocellulose or polyethylene terephthalate) that includes an immobilized detection agent specific for the analyte. The porous membrane adheres to an LC array, which is the transducer responsible for providing the quantitative signal when the recognition complex is formed. The combination of porous membrane and LC arrays is referred to as an inductive test strip throughout the text. A method is provided for detecting the presence of an analyte of interest in a test liquid sample.The test methodology consists of completely immersing the inductive test strip for a variable time of approximately 5 minutes in a liquid sample; it is then removed from the container by placing the edge of the strip on the mouth of the container to remove excess liquid. The strip is then left to rest for a variable time of approximately 2 minutes, and finally the frequency of the LC networks is measured. To ensure the reproducibility of the system, it is recommended to dry the edge of the strip on absorbent paper. Additionally, a signal amplification stage can be included using a sandwich format by immersing the strip in a solution with a labeled receptor (2), which would allow the detection of small molecules.

[0097] This method allows for the rapid, simple, and quantitative determination of pathological components, such as glucose, protein, and similar substances, in body fluids such as urine, serum, and the like. Furthermore, this method also allows for the reagent-free detection of analytes in aqueous solutions such as drinking water, irrigation water, or ambient wastewater in near real time. This type of measurement is a very important element in process control.

[0098] The test strips according to the present invention are particularly useful for the detection of bodily fluids, especially urine; however, since they do not require reagents, they can also have quite general applicability. Obviously, in turbid liquids, such as blood or urine with a high sediment content, the detection methodology must incorporate a washing process before performing the frequency measurement.

[0099] Unlike many strip-based assays currently available, the system described here does not require reagents. The presence and / or quantification of the analyte can be achieved either directly or after one or more reagent addition steps. The absence of the large number of reagents present in conventional strips simplifies device manufacturing, further reducing costs.

[0100] In a third embodiment of the system of the invention, the system of the invention makes use of lateral flow strips. The first lateral flow strip was developed to detect the pregnancy hormone, and since then this type of strips have been developed for multiple analytes; both molecules (cocaine, THD...) and pathogens (viruses, bacteria,

[0101] However, the interest of the strips is not only in obtaining a binary Yes / No response, but in being able to quantify the amount of the analyte of interest by transforming the line / spot generated into an electrical signal that can be processed.

[0102] To date, the most common method for quantifying the amount of an analyte in strips (where a redox reaction is not involved) is generally using various optical methods in which the signal is obtained by refraction or after image processing and intensity measurement in RGB or CiELab coordinates. Recently, strip readers have been developed that use magnetic (or supramagnetic) particles that quantify the magnetic field generated by the accumulation of these particles in the different test lines of lateral flow strips.

[0103] The purpose of the present invention is to quantify the signal obtained from lateral flow strips using LC arrays. The device consists of an LC array with inductors located just below the test and control lines of the lateral flow strips. The detection principle of the inductive sensor is thus based on the changes in the dielectric properties and conductivity resulting from the formation of the recognition complex formed in the control and test lines. This change is due to the nanoparticles (e.g., gold or carbon) and / or analytes bound to these lines when they become visible. The specificity of this system is determined by the specificity of the receptors (2) used in the strip.

[0104] A system is provided for detecting the presence of an analyte, or component, of interest in a sample, preferably a biological sample, wherein the system comprises a lateral flow assay device and an LC array transducer, inductive lateral flow strip.

[0105] The assay device comprises: (a) a sample receiving region; and (b) a capture membrane including a test region comprising an immobilized detection agent specific for the analyte, and a control region including an immobilized reagent that binds to the detection agent. The lateral flow assay device may also include a reservoir region located downstream of the capture membrane to absorb excess fluid, such as excess of the biological sample, liquid formulation of a conjugated indicator, or excess of a chase buffer that can be used with the assay device. The capture membrane is positioned over the coil (1) of the LC array which is the transducer responsible for providing the quantitative signal when the recognition complex is formed.

[0106] A method is provided for detecting the presence of an analyte of interest in a liquid test sample. Such method comprises: a) using an inductive lateral flow strip; b) applying the sample onto the receiving region of the strip thereby dissolving any buffers and / or reagents present therein; c) migrating the liquid phase through the strip and passing a carbon conjugate through a liquid zone into the sample receiving region to form an analyte-conjugate complex, which can also be label-free; (f) allowing the analyte-conjugate complex (or analyte) to migrate along the strip where the analyte comes into contact with the detection agent in the test line, thereby immobilizing the analyte-conjugate complex (or analyte). In this way, upon formation of the recognition complex, a detectable signal can be obtained through LC networks, wherein the formation of the signal indicates the presence of the analyte in the sample.The possibility of having a control zone is at the discretion of the developer and his interests.

[0107] Although the specific embodiment described above employs a carbon particle system as the detection system, it is appreciated that the detection system used in the assay system described herein may be any particulate and / or non-particulate system capable of generating signals that can be detected visually and / or with the aid of LC networks. In addition, a fluidics system may be employed that allows for easy automation and control of the entire process.

[0108] Unlike many lateral flow assays currently available, inductive lateral flow strips do not require nanoparticle-labeled analytes. Instead, the system can respond directly to the presence of analyte in the test lines. The absence of nanoparticles simplifies device manufacturing, further reducing costs, especially when compared to commercial systems with optical detection.

[0109] The system has been successfully tested using test strips in which the test lines were made of carbon nanoparticles (Figure 3). However, the designed device is very versatile and allows the detection of pathogens and analytes. In all cases, detection is achieved through the use of receptors (2) specific to each analyte of interest.

[0110] Also shown in Figure 4 is a successfully performed test using test strips in which the test lines were made with gold nanoparticles.

Claims

1. Analyte detection system comprising: - one or more LC circuits (1 ) comprising: a flat coil (LS) and a capacitor (CT); - at least one receptor (2) arranged on the coils (LS) of the LC circuits (1) and configured to interact with a specific analyte, forming a recognition complex; and - at least one detection device connected to the LC circuits (1 ) and configured to determine variations in the resonance frequency of the LC circuits (1 ) when the recognition complex is formed, thus indicating the presence of the analyte.

2. System according to claim 1, wherein the receiver forms a self-assembled monolayer on the coils (LS) of the LC circuits (1).

3. System according to claim 1, wherein the at least one detection device is connected to the LC circuits (1) by means of a wireless communication module.

4. System according to claim 1, comprising multiple LC circuits (1) that form LC networks.

5. Analyte detection system comprising: - one or more LC circuits (1 ) comprising: a capacitor (CT) and a flat coil (LT); - at least one receptor (2) configured to interact with a specific analyte, forming a recognition complex; - a test strip made of porous material, comprising: a first side, on which the LC circuits (1) are arranged, and a second side, to which at least one receptor (2) is adhered; and - at least one detection device connected to the LC circuits (1 ) and configured to determine variations in the resonance frequency of the LC circuits (1 ) when the recognition complex is formed, thus indicating the presence of the analyte.

6. System according to claim 5, wherein the test strip is made of nitrocellulose or polyethylene terephthalate.

7. Analyte detection system comprising: - one or more LC circuits (1 ) comprising: a capacitor (CT) and a flat coil (LT); - at least one receptor (2) configured to interact with a specific analyte, forming a recognition complex; - at least one lateral flow strip, comprising: a first face, comprising a receptor region and a capture region, defined by one or more capture lines to which the at least one receptor (2) adheres, and / or a second face, on which the LC circuits (1) are arranged in a position corresponding to the position of the capture lines; and - at least one detection device connected to the LC circuits (1 ) and configured to determine variations in the resonance frequency of the LC circuits (1 ) when the recognition complex is formed, thus indicating the presence of the analyte.

8. System according to claim 7, wherein the lateral flow strip further comprises a reservoir region located at an opposite end of the strip to the receiving region.

9. System according to claim 7, wherein the at least one receptor (2) is an immobilized detection agent adhered to the test and / or control line of the lateral flow strip.

10. System according to claim 7, further comprising a conjugate of gold or carbon nanoparticles located on the receptor (2) to amplify the variations in the resonance frequency of the LC circuits (1) when the recognition complex is formed.

11. Analyte detection method comprising the steps of: - provide one or more LC circuits (1 ) comprising: a capacitor (CT) and a flat coil (LT); - having at least one receptor (2) configured to interact with a specific analyte, forming a recognition complex, in contact with the LC circuit (1); - determine variations in the resonance frequency of the LC circuit (1 ) when the recognition complex is formed by means of a detection device connected to the LC circuit (1 ).

12. Analyte detection method comprising the steps of: - provide one or more LC circuits (1 ) comprising: a capacitor (CT) and a flat coil (LT); - provide at least one receptor (2) configured to interact with a specific analyte, forming a recognition complex; - provide one or more test strips made of porous material; - adhere the LC circuits (1 ) to a first side of the test strips; - arranging the at least one receiver (2) on a second side of the test strip in a position corresponding to the position of the LC circuit (1); - immerse the test strips in a sample fluid to form the recognition complex; and - determine variations in the resonance frequency of the LC circuit (1 ) when the recognition complex is formed by means of a detection device connected to the LC circuit (1 ).

13. Method according to claim 12, further comprising a step of amplifying a signal from the detection device generated by the variation in the resonance frequency of the LC circuit (1) by means of a sandwich format, immersing the strip in a solution with a marked receiver (2).

14. Method according to claim 12, further comprising a step of washing the sample fluid, prior to the step of immersing the test strips in said sample fluid.

15. Analyte detection method comprising the steps of: - provide one or more LC circuits (1 ) comprising: a capacitor (CT) and a flat coil (LT); - provide at least one receptor (2) configured to interact with a specific analyte, forming a recognition complex, in contact with the LC circuit (1); - providing one or more lateral flow strips, comprising a first side comprising, in turn, a receiving region and a capture region, defined by one or more capture lines; - adhere the at least one receiver (2) to the capture lines of the lateral flow strip, - adhere the LC circuits (1 ) to a second face in a position corresponding to the position of the capture lines; - depositing a sample fluid in the receiving region of the lateral flow strips for its migration towards the capture lines and to form the recognition complex; and - determine variations in the resonance frequency of the LC circuit (1 ) when the recognition complex is formed by means of a detection device connected to the LC circuit (1 ).

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