Radio frequency sensor for instantaneous wireless biomarker detection

Abstract

Provided herein are systems, devices, and methods for radio frequency sensors for transient wireless biomarker detection.

Description

Background Technology

[0001] This invention generally relates to an on-the-spot device for measuring various biomarkers in blood or urine. Therefore, a variety of applications are possible, including creatinine detection, etc. There is currently a need for rapid and accurate biomarker detection.

[0002] This invention attempts to solve these problems, as well as others. Summary of the Invention

[0003] This article provides systems, apparatus, and methods for radio frequency sensors used for transient wireless biomarker detection.

[0004] The methods, systems, and apparatuses are set forth in part in the following description and will be apparent in part from the description, or may be learned by practice of the methods, apparatuses, and systems. The advantages of the methods, apparatuses, and systems will be realized and obtained by means of the elements and combinations particularly pointed out in the appended claims. It should be understood that the foregoing general description and the following detailed description are exemplary and illustrative only, and not intended to limit the claimed methods, apparatuses, and systems. Attached Figure Description

[0005] In the accompanying drawings, in several preferred embodiments of the invention, the same elements are identified by the same reference numerals.

[0006] Figure 1A This is a front perspective view of the sensor, showing two 2-turn excitation spirals and the FR 4 base; Figure 1B This is a front perspective view of the sensor, showing a slotted conductive layer, microstrip lines, and a ground plane. The dual-port double-helix structure exhibits a cylindrical geometry. The double-helix features an improved internal structure to enhance sensing. Figure 1C This is a curve of the sensor's S11 amplitude.

[0007] Figure 2A This is a front perspective view showing the outer layer of the two-port double-strand helical structure; Figure 2B This is a front perspective view of the sensor, showing the second layer concentrically wrapped by the outer layer; Figure 2C It is a front perspective view of the third layer and multiple slots within the inner metal cylinder; and Figure 2D It is a bottom perspective view of the supporting structure.

[0008] Figure 3A The outer layer is the first layer, consisting of a double-helix structure with N=3 turns. The double-helix structure has a width a=2 mm, thickness=1 mm, height h=33.7 mm, and pitch=9.9 mm; and Figure 3BIt is a side sectional view of multiple grooves in the third layer and the inner metal cylinder, including N=1 turn, pitch=24 mm, height h=33.7 mm, thickness=1 mm, spacing between the outer grooves b=4 mm and width c=8 mm.

[0009] Figure 4A This is a front perspective view showing the sensors in the second and fourth layers; Figure 4B yes Figure 4A The enlarged portion shows the base structure and grounding plate.

[0010] Figure 5 This is a photo of a sensor 3D printed using additive manufacturing technology in a PCB manner.

[0011] Figure 6A It is the surface distribution of the current density of the sensor; and Figure 6B It refers to the electric field distribution of the sensor.

[0012] Figures 7A-7C Here is a photograph showing the test of an artificial blood plasma sample: ( Figure 7A Keysight's FieldFox RF Vector Network Analyzer N9914A, Figure 7B The empty sensor connected to the VNA, Figure 7C A sensor loaded with an artificial plasma sample.

[0013] Figures 8A-8D This is a graph showing the S11 amplitude of the sensor used for artificial plasma samples with different creatinine levels. Figure 8E This is a graph showing the predicted values ​​of creatinine concentration compared to reference values ​​for ten randomly shuffled test / training datasets used for Gaussian process regression, resulting in a mean absolute relative difference (MARD) of approximately 8.54%.

[0014] Figures 9A-9C This is a photograph of an artificial urine sample used for testing: ( Figure 9A Keysight Technologies' FieldFox RF Vector Network Analyzer N9914A, Figure 9B () Connect to the empty sensor of the VNA, ( Figure 9C A sensor loaded with an artificial urine sample.

[0015] Figures 10A-10B This is a graph showing the amplitudes of S11 and S21 of the sensor for artificial urine samples with different creatinine levels.

[0016] Figure 11A-11BThis is a graph showing the sensor's response to changes in creatinine during artificial urine testing. The S11 amplitude at different frequencies is compared to the reference creatinine level: ( Figure 11A Approximately 4 GHz and ( Figure 11B Approximately 4.225 GHz. The green line is the S11 fitting curve, showing the sensor's response trend as creatinine concentration increases.

[0017] Figure 12 This is a graph showing the predicted creatinine concentration in artificial urine compared to the reference creatinine level, where MARD is approximately 11.96%.

[0018] Figure 13A This is a graph showing the predicted creatinine concentration compared to the reference creatinine level in urine samples collected from rats at baseline. Figure 13B This is a graph showing the predicted creatinine concentration compared to the reference creatinine level in urine samples collected from rats one month after injection. Figure 13C This is a graph showing the predicted creatinine concentrations compared to reference creatinine levels in urine samples collected from rats 2 months after injection, with predicted MARDs of approximately 6.94%, 10%, and 7.28%, respectively.

[0019] Figure 14 This is a graph showing the predicted creatinine concentration in human urine compared to a reference creatinine level, where MARD is approximately 7.3%.

[0020] Figure 15 This is a graph showing the predicted creatinine concentration in human plasma compared to the reference creatinine level, where MARD is approximately 3.28%. Detailed Implementation

[0021] The foregoing and other features and advantages of the invention will become apparent from the following detailed description of exemplary embodiments, which are read in conjunction with the accompanying drawings. The detailed description and drawings are merely illustrative and not limiting of the invention, the scope of which is defined by the appended claims and their equivalents.

[0022] Embodiments of the invention will now be described with reference to the accompanying drawings, wherein the same numerals consistently reflect the same elements. The terminology used in the description herein is not intended to be limited or restrictive in any way, simply because it is used in conjunction with a detailed description of certain specific embodiments of the invention. Furthermore, embodiments of the invention may include several novel features, none of which alone is responsible for its desired properties or is essential for practicing the invention described herein.

[0023] Unless otherwise stated herein or clearly contradicted by the context, the terms “a,” “an,” “the,” and “the,” and similar designations used in the context of describing the invention should be interpreted as encompassing both the singular and plural. It will also be understood that the terms “comprises,” “comprising,” “includes,” and / or “including”, when used herein, specify the presence of the stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0024] Unless otherwise stated herein, the descriptions of numerical ranges herein are intended only as a shorthand method for individually referring to each individual value falling within the range, and each individual value is incorporated into the specification as if it were individually described herein. When accompanied by numerical values, the word “about” should be interpreted as indicating a deviation from the stated value of up to and including 10%. Unless otherwise required, the use of any and all instances or exemplary language (“e.g.” or “such as”) provided herein is intended only to better illustrate the invention and does not constitute a limitation on the scope of the invention. Nothing in this specification should be construed as indicating that any unclaimed element is necessary for the practice of the invention.

[0025] References to "one embodiment," "implementation," "example embodiment," "various embodiments," etc., may indicate that one or more embodiments of the invention described herein may include a particular feature, structure, or characteristic, but not every embodiment must include that particular feature, structure, or characteristic. Furthermore, the repeated use of the phrase "in one embodiment" or "in an exemplary embodiment" does not necessarily refer to the same embodiment, although they may be the same embodiment.

[0026] As used herein, the term "method" means the manner, means, technique, and procedure for accomplishing a given task, including but not limited to those manner, means, techniques, and procedures known to or readily developed from known manner, means, techniques, and procedures in the fields of chemistry, electricity, biology, biochemistry, mechanics, and medicine. Unless otherwise expressly stated, no method or aspect set forth herein is intended to be construed as requiring its steps to be performed in a particular order. Therefore, no order is intended to be inferred in any aspect unless a method claim specifically states in the claim or description that the steps will be limited to a particular order. This applies to any possible non-express basis of interpretation, including logical questions concerning the arrangement of steps or operational procedures, simple meanings derived from grammatical organization or punctuation, or the number or type of aspects described in the specification.

[0027] Description of the implementation method Generally, the radio frequency sensor 100 used for transient wireless biomarker detection includes a two-port, double-strand helical structure exhibiting a cylindrical geometry, such as... Figure 1A As shown. The double helix has an improved internal structure to enhance sensing. In one embodiment, the sensor is a 3D structure that has volumetric sensitivity rather than planar sensitivity to changes in the composition of urine and blood.

[0028] A method for transient wireless detection of biomarkers includes: using a structure based on a dual-port double-helix antenna, and including an improved internal structure to enhance sensing by utilizing the dual-port double-helix structure; detecting the composition of urine or blood by using volumetric sensitivity to changes in composition of urine or blood instead of planar sensitivity. The method further includes: wrapping four cylindrical layers concentrically around each other; including an outer layer in the dual-port double-helix structure, the outer layer wrapping around a second layer; including a plastic cylindrical column and a volumetric structure in the second layer; placing a third layer inside the plastic cylindrical column, the third layer being composed of a conductive metal inner cylinder, serving as a sensing layer of a sensor, and including a plurality of slots in the conductive metal inner cylinder; disposing a fourth layer within the third layer, and including a plastic tube within the sensing layer, and holding a sample in the plastic tube during measurement.

[0029] The method further includes a two-port double-strand helix structure as an external feeder helix having two 3-turn helices radiating in the azimuth direction. The method further includes orienting multiple slots in the conductive metal inner cylinder orthogonal to the rotational orientation of the two-port double-strand helix structure to enhance sensing, and allowing radiation from the two-port double-strand helix structure, including reflected fields from the conductive metal inner cylinder, to leak through the multiple slots to amplify sensing capabilities and focus the signal onto the internal test of the fourth layer.

[0030] The method further includes supporting the cylindrical section by a base structure comprising a 2D layer including a feed network, a dielectric substrate, and a ground plane. The method further includes using a cylindrical slot as a complementary open-circuit resonator and instantaneously detecting the concentration of urine components via electromagnetic radiation; wherein the urine components include creatinine, ammonia, urea, or uric acid; and detecting creatinine levels between approximately 0.2 mg / dL and approximately 4 mg / dL.

[0031] The method further includes utilizing multiple slot leaks in the conductive metal inner cylinder to induce a multi-band response, enabling enhanced sensitivity monitoring of creatinine levels across multiple frequency bands. The method further includes providing a surface distribution of current density and an electric field distribution on the inner surface of the slotted metal cylinder surrounding the sample, showing highly concentrated regions around the slots of the sensor's inner metal cylinder at different frequencies, including regions highly sensitive to changes in the composition of the loaded sample.

[0032] like Figure 1A-1B As shown, the sensor 100 includes a volumetric cylindrical tube comprising four cylindrical layers that surround each other and are disposed on a base 200. An outer layer 110 concentrically surrounds a second layer 120, the second layer 120 concentrically surrounds a third layer 130, and the third layer 130 concentrically surrounds a fourth layer. The outer layer 110 consists of a double-helix structure 112 comprising two three-turn excitation helices 114. The double-helix structure 112 surrounds the second layer 120, which is composed of PLA plastic cylindrical pillars, as shown... Figure 3B As shown in Figure 3C, the conductive metal inner cylinder 120 is the sensing layer of the sensor system and includes multiple slots 134. The third layer 130 consists of a conductive metal inner cylinder 132 located inside a PLA plastic cylindrical column. The fourth layer 140 consists of a PLA plastic tube inside the conductive metal inner cylinder 132. The PLA plastic tube is placed within the sensing volume of the sensor and is responsible for holding the sample during measurement.

[0033] Figure 1B This is a front perspective view of the sensor, showing a slotted conductive layer, microstrip lines, and a dual-port, double-helix structure with a cylindrical geometry. The double-helix features an improved internal structure to enhance sensing. Figure 1C This is a curve of the sensor's S11 amplitude.

[0034] like Figure 3A As shown, the external double-helix structure 112 is an external feed helix, which consists of two 3-turn helices 114 radiating in the azimuth direction. The external double-helix structure 112 terminates on the base 200 with a feed line 116. As shown in FIG. 3C, the third cylinder 130 includes a plurality of slots 134 orthogonal to the rotational orientation of the outer helix structure 112 to enhance sensing. Radiation from the feed helix (including reflected fields from the slotted metal layer 130) will leak through the slots, which amplifies the sensing capability. This allows the signal to be focused onto internal test equipment.

[0035] like Figure 2D As shown, the cylindrical sensor 100 is supported by a base structure 200, which consists of a 2D layer including a feeding network 116 (two microstrip lines 202 feeding a spiral), a dielectric substrate (FR4), and a ground plane 204.

[0036] The volumetric cylindrical tube consists of four cylindrical layers that are coaxially wrapped around each other. In one embodiment, the outer layer has dimensions including a radius of about 8 mm, a height of about 33.7 mm, and a thickness of about 1 mm. The second layer has dimensions including a radius of about 6.01 mm, a height of about 33.7 mm, and a thickness of about 2 mm. The third layer has dimensions including a radius of about 5.01 mm, a height of about 33.7 mm, and a thickness of about 1 mm. The fourth layer has dimensions including a radius of about 3.01 mm, a height of about 33.7 mm, and a thickness of about 2 mm. Alternative dimensions may be included, as long as the cylindrical layers are coaxially wrapped around each other.

[0037] like Figure 3B As shown, the cylindrical trough is a complementary open-circuit resonator used to instantaneously detect the concentration of urine components via electromagnetic radiation. Urine components include, but are not limited to, creatinine, ammonia, urea, and uric acid.

[0038] Figure 3A The first layer consists of a double-helix structure with N=3 turns. The double-helix structure has a width a = approximately 2 mm, a thickness of approximately 1 mm, a height h = approximately 33.7 mm, and a pitch of approximately 9.9 mm; and Figure 3B It is a side sectional view of multiple slots within the third layer and the inner metal cylinder, including N=1 turn, pitch=approx. 24 mm, height h=approx. 33.7 mm, thickness=approx. 1 mm, spacing between outer slots b=approx. 4 mm, and width c=approx. 8 mm. Alternative dimensions may be included, as long as the number of turns N remains consistent.

[0039] In one implementation, the sensor is designed to operate in a lower microwave frequency band between approximately 4 GHz and approximately 6.5 GHz.

[0040] like Figures 4A-4B As shown, the second layer 120 serves as a substrate separating the two conductive layers 1 and 3. The second layer is made of PLA plastic and its dimensions include a height h = approximately 33.7 mm and a thickness of approximately 2 mm. The fourth layer 140 serves as a sample holder and is also made of PLA plastic. The dimensions of the fourth layer 140 include a height h = approximately 33.7 mm and a thickness of approximately 2 mm. The base structure 200 includes a 2D layer comprising a feed network, a dielectric substrate (FR4) 202, and a ground plane 204. The base structure 200 includes a width w = approximately 30 mm and a thickness t = approximately 0.8 mm. Alternative dimensions may be included, as long as the cylindrical layers are coaxially wrapped around each other.

[0041] The sensing tube is surrounded by multiple slots, resulting in a multi-band response, which allows for monitoring of creatinine levels across multiple frequency bands with enhanced sensitivity.

[0042] like Figures 6A-6B As shown, the surface current density (Jsurf) and electric field (E-field) distributions on the inner surface of the slotted metal cylinder surrounding the sample reveal a highly concentrated region around the slot at different frequencies, suggesting a region highly sensitive to changes in the composition of the loaded sample. The E-field comprises a surface current density (Jsurf) of approximately 3000.195 V / m and 10 A / m on the inner surface of the slotted metal cylinder. Antenna surface current density. When the urine sample to be tested is loaded into the sensor, a computer program is used to analyze the two signals measured from the sensor. This computer program uses regression modeling techniques to map the recorded scattering parameters (amplitude and phase) to the concentration of the urine sample components.

[0043] The sensor system was designed to show a high correlation between the S-parameter response recorded when the sensor was loaded with urine or blood samples and the changes in the concentration of components in the loaded samples.

[0044] The sensor was tested in preclinical and clinical settings and reported high sensitivity to changes in creatinine concentration in urine or blood samples. The experiments conducted support and enable the sensor to accurately detect creatinine concentrations in loaded samples.

[0045] like Figure 5 As shown, the outer layer 110 and the third layer 130 were 3D printed in a PCB manner using additive manufacturing technology. Aluminum (AlSi10Mg) was used in conjunction with selective laser melting (SLM) technology to perform the 3D printing. The second layer 120 and the third layer 130 were 3D printed using PLA plastic material. The base structure 200 was fabricated on an FR4 epoxy substrate using an LPKF S63 CNC milling machine.

[0046] Other detectable biomarkers include new / exotic / malignant or non-malignant cells or other newly developed molecules that may not be part of the typical components of a biological system. Biomarkers can be tracked not only in the blood but also in other parts of the biological system, such as saliva, tissues, etc.

[0047] As used herein, biomarker is a broad term and is given its common and conventional meaning to those skilled in the art (and not limited to a specific or customized meaning), and further refers to, but not limited to, substances or chemical components in analyzable biological fluids (e.g., blood, interstitial fluid, cerebrospinal fluid, lymph, or urine). Biomarkers can include naturally occurring substances, artificial substances, metabolites, and / or reaction products. In some embodiments, a biomarker is a biomarker used for measurement by sensors, devices, and methods. However, other biomarkers have also been envisioned, including but not limited to: prothrombin; acylcarnitine; adenine phosphoribosyltransferase; adenosine deaminase; albumin; alpha-fetoprotein; amino acid profile (arginine (Krebs cycle), histidine / uric acid, homocysteine, phenylalanine / tyrosine, tryptophan); androstenedione; antipyrine; arabinitol enantiomers; arginase; benzoylecone (cocaine); biotinamidase; biopterin; C-reactive protein; carnitine; pre-BNP; BNP; troponin; carnosine; CD4; ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol; cholinesterase; conjugated protein. 1-β-hydroxycholic acid; cortisol; creatine kinase; creatine kinase MM isoenzyme; cyclosporine A; d-penicillamine; deethylchloroquine; dehydroepiandrosterone sulfate; DNA (acetylation polymorphism, alcohol dehydrogenase, α1-antitrypsin, cystic fibrosis, Duchenne muscular dystrophy / Becker muscular dystrophy, analyte-6-phosphate dehydrogenase, hemoglobin A, hemoglobin S, hemoglobin C, hemoglobin D, hemoglobin E, hemoglobin F, D-Punjab, β-thalassemia, hepatitis B virus, HCMV, HIV-1, HTLV-1, Leber hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax Vivax), sexual differentiation, 21-deoxycortisol); desbutylhalofantrine; dihydropteridine reductase; diphtheria / tetanus antitoxin; erythrocyte arginase; erythrocyte protoporphyrin; esterase D; fatty acid / acylglycine; free β-human chorionic gonadotropin; free erythrocyte porphyrin; free thyroxine (FT4); free triiodothyronine (FT3); fumarate acetylacetyltransferase tase); galactose / gal-1-phosphate; galactose-1-phosphate uridine transferase; gentamicin; analyte-6-phosphate dehydrogenase; glutathione; glutathione peroxidase; glycocholic acid; glycated hemoglobin; halofantoride; hemoglobin variants; aminohexosidase A; human erythrocyte carbonic anhydrase I; 17-α-hydroxyprogesterone; hypoxanthine phosphoribosyltransferase; immunoreactive trypsin; lactate; lead; lipoprotein ((a), B / A-1, β); lysozyme; mefloquine; netilmicin;Phenobarbital; Phenytoin; Phytanic acid / norphytanic acid; Progesterone; Prolactin; Aminoacylproline dipeptidase; Purine nucleoside phosphorylase; Quinine; Reverse triiodothyronine (rT3); Selenium; Serum pancreatic lipase; Sissomicin; Somatostatin C; Specific antibodies (Adenovirus, Antinuclear antibody, Anti-ζ antibody, Arbovirus, Aujeszky virus, Dengue virus, Dracnila medina, Echinococcus granulosus, Entamoeba histolytica, Enterovirus, Giardia duodenalis) Helicobacter pylori, Hepatitis B virus, Herpes simplex virus, HIV-1, IgE (atopic disease), Influenza virus, Leishmania donovani, Leptospira, Measles / mumps / rubella, Mycobacterium leprae, Mycoplasma pneumoniae, Myoglobin, Filococcus spiralis, Parainfluenza virus, Plasmodium falciparum, Poliovirus, Pseudomonas aeruginosa, Respiratory syncytial virus, Rickettsia (scrub typhus), Schistosoma mansoni, Toxoplasma gondii, Treponema pallidum (T) (repenomapallidium), Trypanosoma cruzi / Trekk's trypanosoma, vesicular stomatitis virus, filariasis bancroftian, yellow fever virus); specific antigens (hepatitis B virus, HIV-1); succinylacetone; sulfadoxine; theophylline; thyroid-stimulating hormone (TSH); thyroxine (T4); thyroxine-binding globulin; trace elements; transferrin; UDP-galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A; leukocytes; and zinc protoporphyrin. In some embodiments, naturally occurring salts, sugars, proteins, fats, vitamins, and hormones in blood or interstitial fluid can also constitute biomarkers. Biomarkers can exist naturally in biological fluids, such as metabolites, hormones, antigens, antibodies, etc. Alternatively, biomarkers can be introduced into the body, such as contrast agents for imaging, radioactive isotopes, chemical reagents, fluorocarbon-based synthetic blood, or drugs or pharmaceutical compositions, including but not limited to insulin; ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorinated hydrocarbons, hydrocarbons); cocaine (quick cocaine); stimulants (amphetamines, methamphetamines, ritalin, pemoline). Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine; inhibitors (barbiturates, methaqualone, sedatives such as Valium, Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens (phencyclidine, lysergic acid, mescaline, peyote, psilocybin);Anesthetics (heroin, codeine, morphine, opium, meperidine, percocet, percodan, Tussionex, fentanyl, Darvon, Talwin, Lomotil); designer drugs (fentanyl, meperidine, amphetamines, methamphetamines, and analogues of phencyclohexylpiperidine, such as Ecstasy); anabolic steroids; and nicotine. Metabolites of drugs and drug compositions are also considered biomarkers. Biomarkers generated in the body, such as neurochemicals and other chemicals, such as ascorbic acid, uric acid, dopamine, norepinephrine, 3-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5HT), and 5-hydroxyindoleacetic acid (FHIAA), can also be analyzed.

[0048] Regression model The sensor is connected to a vector network analyzer (VNA) to record its amplitude and / or phase response to changes in the concentration of biomarker components loaded onto blood or urine samples. The experimental procedure is as follows: Data collection, i.e., the measurement of the sensor's S-parameter response. The acquired data consists of the amplitude and phase of S11, S21, and S22, which correspond to different frequencies obtained from the VNA in the range of approximately 4 to approximately 6.5 GHz, such as... Figure 1C As shown.

[0049] Data preprocessing: Each VNA measurement includes the average of 10 readings to avoid the random noise inherent in the VNA.

[0050] Sampling: To minimize redundancy between recorded features, the frequency range is sampled in frequency steps of approximately 0.0625 GHz over an operating frequency range of approximately 4 GHz to approximately 6.5 GHz.

[0051] Normalization: For each feature, the value of the S-parameter amplitude or phase is normalized to a value between 0 and 1.

[0052] The resulting data was then used to train a Gaussian process (GP) regression model, which maps device parameters to estimate the concentration of the desired biomarker.

[0053] This model relies on S-parameter values ​​obtained at a critical frequency identified by a wrapper feature selection technique. In one implementation, a forward feature selection (FFS) wrapper method is used, which selects an optimal subset of features based on the regression model output. The initial optimal subset has zero features, and for each iteration, the feature that provides the lowest average error of the model output is added to the subset. Although this feature selection method is computationally expensive, it can provide excellent selection of sensitive features.

[0054] Example The following embodiments are provided to provide those skilled in the art with a complete disclosure and description of how to prepare and evaluate the compounds, compositions, articles, apparatus, and / or methods claimed herein, and these embodiments are intended purely as examples of the invention and not to limit the scope of what the inventors consider to be their invention. However, based on this disclosure, those skilled in the art should understand that many changes can be made to the specific embodiments disclosed without departing from the spirit and scope of the invention, and still obtain the same or similar results.

[0055] While efforts have been made to ensure the accuracy of figures (e.g., quantities, temperatures, etc.), some errors and deviations should be taken into account. Unless otherwise stated, parts are parts by weight, temperatures are °C or ambient temperature, and pressures are atmospheric pressure or close to atmospheric pressure.

[0056] Example 1: Experiment on artificial blood plasma samples Figures 7A-7C This is a diagram showing the testing of artificial blood plasma samples: ( Figure 7A Keysight Technologies' FieldFox RF Vector Network Analyzer N9914A, Figure 7B The empty sensor connected to the VNA, Figure 7C A sensor loaded with an artificial plasma sample.

[0057] Figures 8A-8D This is a graph showing the S11 amplitude of the sensor for artificial plasma samples with different creatinine levels and frequencies between 4 Hz and 6.5 Hz. The S11 amplitude at 4.5 Hz is between approximately -8 [dB] and approximately -5 [dB], as shown. Figure 8B As shown. The S11 amplitude at 5.5 Hz is between approximately -7 [dB] and approximately -4 [dB], as... Figure 8C As shown. The S11 amplitude at 5.0 Hz is between approximately -3 [dB] and approximately -2 [dB], as... Figure 8D As shown. Figure 8EThis is a graph showing the predicted values ​​of creatinine concentration compared to reference values ​​for ten randomly shuffled test / training datasets used for Gaussian process regression, resulting in a mean data error or mean absolute relative difference (MARD) of approximately 8.54%, where R0 2 = Approximately 0.98. Embodiments of this sensor detected creatinine levels of 119.30 mg / dl, 322.17 mg / dl, 538.26 mg / dl, 711.14 mg / dl, and 840.79 mg / dl. Mean Absolute Relative Difference (MARD) is a statistical measure that compares the accuracy of a sensor or other device to a reference measurement. MARD is commonly used to assess accuracy. MARD is calculated as the absolute difference between the average sensor measurement and the reference measurement. MARD is reported as a percentage. A lower MARD indicates better consistency between the sensor and the reference measurement.

[0058] Example 2: Experiment on artificial urine samples Figures 9A-9C The testing apparatus for artificial urine samples is shown: ( Figure 9A Keysight Technologies' FieldFox RF Vector Network Analyzer N9914A, Figure 9A The empty sensor connected to the VNA, Figure 9C A sensor loaded with an artificial urine sample.

[0059] Figures 10A-10B This is a graph showing the S11 and S21 amplitudes of the sensor for artificial urine samples with different creatinine levels. At frequencies between approximately 4 and approximately 6.5 Hz and S11 amplitudes between -3 [dB] and -50 [dB], the creatinine levels detected by the sensor of this invention are: 3.524 mM, 5.071 mM, 6.6 mM, 8.129 mM, 9.658 mM, 11.187 mM, 12.716 mM, 14.245 mM, 15.774 mM, 17.303 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, 30 mM, 35 mM, and 40 mM, as shown. Figure 10AAs shown. At frequencies between 4 and 6.5 Hz and amplitudes between -5 [dB] and -50 [dB] for S21, the sensor of this invention detected creatinine levels of: 3.524 mM, 5.071 mM, 6.6 mM, 8.129 mM, 9.658 mM, 11.187 mM, 12.716 mM, 14.245 mM, 15.774 mM, 17.303 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, 30 mM, 35 mM, and 40 mM, as... Figure 10B As shown.

[0060] Figure 11A-11B This is a graph showing the sensor's response to changes in creatinine during artificial urine testing. The S11 amplitude is compared to the reference creatinine level at different frequencies, ranging from -2.8 [dB] to -3.1 [dB]: ( Figure 11A 4 GHz, for creatinine concentrations between 5 and 40 mM, R 2 It is 0.94; Figure 11B 4.225 GHz, for creatinine concentrations between 5 and 40 mM, R 2 The value is 0.97. The green line is the S11 fitting curve, showing the sensor's response trend as creatinine concentration increases.

[0061] Figure 12 This is a graph showing the predicted creatinine concentration in artificial urine between 5 and 40 mM compared to the reference creatinine level between 5 and 40 mM, where MARD is 11.96% and R... 2 The value was 0.91. This indicates high accuracy in detecting creatinine concentrations in urine between 5 and 40 mM.

[0062] Example 3: In vivo experiments on animal models Figures 13A-13C It is shown that ( Figure 13A The predicted creatinine concentrations in urine samples collected from rats at baseline, ranging from approximately 0.5 mg / dL to approximately 4 mg / dL, were compared with reference creatinine levels ranging from 0 to 4 mg / dL. Figure 13B The predicted creatinine concentrations in urine samples collected from rats one month after injection, ranging from approximately 0.5 mg / dL to approximately 4 mg / dL, were compared with reference creatinine levels ranging from 0 to 4 mg / dL. Figure 13CThe predicted creatinine concentrations at approximately 0.5 mg / dl and approximately 2.5 mg / dl in urine samples collected from rats 2 months after injection were compared with reference creatinine levels between 0 and 2.5 mg / dl, with predicted MARD values ​​of approximately 6.94%, approximately 10%, and approximately 7.28%, respectively.

[0063] Example 4: Clinical Study - Human Urine - Figure 14 This is a graph comparing predicted creatinine concentrations in human urine from approximately 0.2 mg / dl to approximately 4 mg / dl with reference creatinine levels between 0.2 and 4 mg / dl, where MARD is approximately 7.3%.

[0064] Example 5: Clinical Study - Human Serum - Figure 15 This is a graph comparing predicted creatinine concentrations in human plasma between approximately 4 mg / dl and approximately 10 mg / dl with reference creatinine levels between approximately 4 mg / dl and approximately 12 mg / dl, where MARD is approximately 3.28%.

[0065] system The terms "component" and "system" as used in this application are intended to refer to computer-related entities, which can be hardware, a combination of hardware and software, software, or software in execution. For example, a component can be, but is not limited to, a process running on a processor, a processor, an object, an executable file, an execution thread, a program, and / or a computer. For illustration, both an application running on a server and the server itself can be components. One or more components may reside within a process and / or an execution thread, and components may be located on a single computer and / or distributed across two or more computers.

[0066] Generally, program modules include routines, programs, components, data structures, etc., that perform specific tasks or implement specific abstract data types. Furthermore, those skilled in the art will understand that the methods of this invention can be practiced with other computer system configurations, including single-processor or multi-processor computer systems, minicomputers, mainframe computers, personal computers, handheld computing devices, microprocessor-based or programmable consumer electronics, etc., each of which can be operatively coupled to one or more associated devices.

[0067] The aspects illustrated in this invention can also be practiced in a distributed computing environment, where certain tasks are performed by remote processing devices linked via a communication network. In a distributed computing environment, program modules can reside in both local and remote storage devices.

[0068] Computers typically include a variety of computer-readable media. Computer-readable media can be any available medium accessible to a computer, and includes volatile and non-volatile media, removable and non-removable media. By way of example and not limitation, computer-readable media can include computer storage media and communication media. Computer storage media includes volatile and non-volatile, removable and non-removable media implemented in any method or technology for storing information such as computer-readable instructions, data structures, program modules, or other data. Computer storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other storage technologies, CD-ROM, digital versatile disc (DVD) or other optical disc storage, magnetic tape cassettes, magnetic tape, disk storage or other magnetic storage devices, or any other medium that can be used to store desired information and is accessible to a computer.

[0069] Communication media typically embody computer-readable instructions, data structures, program modules, or other data in the form of modulated data signals such as carrier waves or other transmission mechanisms, and include any information transmission medium. The term "modulated data signal" means a signal having one or more of its characteristic sets or altered in a manner that encodes information in the signal. As an example, and not a limitation, communication media include wired media such as wired networks or direct-line connections, and wireless media such as acoustic, RF, infrared, and other wireless media. Any combination of the above should also be included within the scope of computer-readable media.

[0070] Software includes applications and algorithms. Software can be implemented in smartphones, tablets or personal computers, the cloud, wearable devices, or other computing or processing devices. Software can include logs, diaries, spreadsheets, games, recordings, communications, SMS messages, websites, charts, interactive tools, social networks, VoIP (Voice over Internet Protocol), email, and video.

[0071] In some embodiments, some or all of the functions or processes described herein and performed by a computer program are formed in computer-readable program code and embodied in a computer-readable medium. The phrase "computer-readable program code" includes any type of computer code, including source code, object code, executable code, firmware, software, etc. The phrase "computer-readable medium" includes any type of medium that can be accessed by a computer, such as read-only memory (ROM), random access memory (RAM), hard disk drive, optical disc (CD), digital video disc (DVD), or any other type of storage.

[0072] All disclosures and patent applications mentioned in this specification are incorporated herein by reference, as if each individual disclosure or patent application were expressly and individually indicated to be incorporated herein by reference.

[0073] While the invention has been described in conjunction with various embodiments, it should be understood that the invention is capable of further modifications. This application is intended to cover any variations, uses, or modifications of the invention that generally follow the principles of the invention and include deviations from this disclosure within the scope of practice known and customary in the art to which this invention pertains.

Claims

1. A sensor, comprising: Based on the structure of a dual-port double-strand helical antenna, the dual-port double-strand helical structure includes an improved internal structure to enhance sensing; wherein the sensor is a 3D structure with volumetric sensitivity rather than planar sensitivity to changes in the composition of urine and blood.

2. The sensor of claim 1, further comprising four cylindrical layers concentrically wrapped around each other; an outer layer comprising the dual-port double-strand helical structure, the outer layer wrapping around the second layer; the second layer comprising a plastic cylindrical column and a volumetric structure; a third layer inside the plastic cylindrical column, the third layer comprising a conductive metal inner cylinder serving as the sensing layer of the sensor, the conductive metal inner cylinder comprising a plurality of grooves; and a fourth layer within the third layer, the fourth layer comprising a plastic tube placed within the sensing layer of the sensor and responsible for holding the sample during measurement.

3. The sensor according to claim 2, wherein, The dual-port double-strand spiral structure is an externally fed spiral, which consists of two 3-turn spirals that radiate along the azimuth direction.

4. The sensor according to claim 3, wherein, The plurality of grooves in the conductive metal inner cylinder are orthogonal to the rotational orientation of the dual-port double-strand helical structure to enhance sensing, and radiation from the dual-port double-strand helical structure, including the reflected field from the conductive metal inner cylinder, leaks through the plurality of grooves to amplify sensing capability and focus the signal on the internal test of the fourth layer.

5. The sensor according to claim 4, wherein, The cylindrical section is supported by a base structure, which consists of a 2D layer comprising a power supply network, a dielectric substrate, and a ground plane.

6. The sensor according to claim 5, wherein, The cylindrical groove is a complementary open resonator to instantaneously detect the concentration of urine components via electromagnetic radiation; and the urine components include creatinine, ammonia, urea, or uric acid.

7. The sensor according to claim 6, wherein, The sensor operates in a lower microwave frequency band between approximately 4 GHz and approximately 6.5 GHz.

8. The sensor according to claim 7, wherein, Leakage in the plurality of slots in the conductive metal inner cylinder results in a multi-band response, which monitors the creatinine level across multiple frequency bands with enhanced sensitivity.

9. The sensor of claim 8, further comprising a current density surface distribution and an electric field distribution on the inner surface of the slotted metal cylinder surrounding the sample, wherein at different frequencies, the area around the slot of the inner metal cylinder of the sensor exhibits a highly concentrated region, including a region highly sensitive to changes in the composition of the loaded sample.

10. The sensor of claim 9, further comprising, when a urine sample to be tested is loaded into the sensor, using a computer program to analyze two signals measured from the sensor, the computer program utilizing regression modeling techniques to map the recorded scattering amplitude and phase parameters to the concentration of the urine sample components.

11. The sensor of claim 10, further comprising a high correlation between the signal (S-parameter) response measured from the sensor and the concentration change of the component of the loaded sample, recorded when the sensor is loaded with a urine or blood sample.

12. The sensor of claim 10, further comprising high sensitivity to changes in creatinine concentration in urine or blood samples.

13. A method for transient wireless detection of biomarkers, comprising: It uses a structure based on a dual-port double-helix antenna and includes an improved internal structure to enhance sensing by utilizing the dual-port double-helix structure; The composition of urine or blood is detected by using volume sensitivity to changes in the composition of urine or blood, rather than planar sensitivity.

14. The method of claim 13, further comprising: concentrically wrapping four cylindrical layers around each other; including an outer layer in the dual-port double-strand helical structure, the outer layer wrapping around the second layer; the second layer including a plastic cylindrical column and a volume structure; placing a third layer inside the plastic cylindrical column and the third layer consisting of a conductive metal inner cylinder as a sensing layer of the sensor, and including a plurality of grooves in the conductive metal inner cylinder; providing a fourth layer within the third layer, and including a plastic tube within the sensing layer, and holding the sample in the plastic tube during measurement.

15. The method according to claim 14, further comprising assembling the dual-port double-strand helical structure into an externally fed helix having two 3-turn helices radiating in the azimuth direction.

16. The method of claim 15, further comprising orienting the plurality of slots in the conductive metal inner cylinder to be orthogonal to the rotational orientation of the two-port double-strand helical structure to enhance sensing, and allowing radiation from the two-port double-strand helical structure, including a reflected field from the conductive metal inner cylinder, to leak through the plurality of slots to amplify sensing capability and focus the signal onto the internal test of the fourth layer.

17. The method of claim 16, further comprising supporting the cylindrical section by a base structure, the base structure comprising a 2D layer including a power supply network, a dielectric substrate and a ground plane.

18. The method of claim 17, further comprising using the cylindrical groove as a complementary open resonator and instantaneously detecting the concentration of urine components by electromagnetic radiation; and the urine components including creatinine, ammonia, urea, or uric acid; and detecting creatinine between about 0.2 mg / dl and about 4 mg / dl.

19. The method of claim 18, further comprising utilizing the leakage of the plurality of grooves in the conductive metal inner cylinder to cause a multi-band response, thereby monitoring the creatinine level with enhanced sensitivity across multiple frequency bands.

20. The method of claim 19, further comprising providing a current density surface distribution and an electric field distribution on the inner surface of the slotted metal cylinder surrounding the sample, wherein at different frequencies, the area around the slot of the inner metal cylinder of the sensor exhibits a highly concentrated region, including a region highly sensitive to changes in the composition of the loaded sample.

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