KR20220073649A - The platform that rapidly and accurately generates big data of optical signals for material analyses and enables pattern recognitions, storage, and sharing of such data - Google Patents

Abstract

The present invention is a material analysis platform that separates the optical signal of a material present in a trace amount in a sample for analysis from the optical signal of a large amount of material, and accurately measures the types and amounts of all materials in the sample. The optical signal of a trace material to be measured is divided into many regions at a level where the optical signal of a trace material to be measured can be discerned, and when the optical signal is extracted, the material is not allowed to enter and exit at the boundary between each analysis region, so that the optical signal in each region is parallelized It is an analysis platform that allows extraction. Therefore, it is possible to quickly extract and analyze optical signals for all substances in the analysis sample without overlapping and omission between substances used for optical signal extraction of each analysis area. In addition, the analysis platform of the present invention enables the sharing of optical signals and pattern big data. The present invention relates to a substrate on which micro-sized or larger cells for extracting Raman signals and various optical signals (the present inventor calls the cell name Ramcell or RamCell) are repeatedly distributed (the present inventor refers to this substrate as a Ramcell substrate) and Their manufacturing methods, patterns, modules and materials for optical signal amplification inside each Ramcell, modules and operating methods for extracting optical signals from each Ramcell, acquiring, processing, and purifying analytes, and adding analytes to each Ramcell It includes the distribution module and operation method, optical signal big data storage, analysis, sharing module and operation method. Each module may be made by micro-electro-mechanical systems (aka MEMS) technology. In particular, rapid and accurate laser generation, optical signal extraction and analysis, etc. are possible through the parallel optical signal extraction and analysis module (the present inventor refers to this module as a RamCell processing unit or RamCell Processing Unit, also known as RPU). The present invention can be used for extracting various optical signals, but for the purpose of explaining the present invention, a Raman signal among various optical signals is focused on. Therefore, all bills, specific contents, and parts that mention the Raman signal in the drawings are not limited to the Raman signal.
The present invention enables the generation and amplification of Raman signals with high reproducibility, and rapid and precise Raman signal extraction and analysis through standardized Ramcells for Raman signals of numerous substances as well as trace substances in samples for analysis. Through the present invention, the frequency and range of the Raman spectrum peak representing each material according to each temperature, pressure, composition of the sample, characteristics of laser and LED, and Ramcell structure, and the concentration of each material (or the number of molecules in the sample) ), it is possible to form a library by collecting big data of the Raman spectrum that standardizes the size and range of the peaks. Other variables related to substances can also be made into big data. For example, when the sample for analysis is blood, various information about the body from which the blood is extracted and psychological, social, economic, geographical factors related to the subject of the body may also be included. More specifically, the age, weight, race, family history, stress level, living location, occupation, etc. of the subject of the body may be the independent variables related to the spectrum. Using the big data library of optical signal spectra of each pure substance and mixture, each spectral pattern recognition model can be formed. The present invention includes a library of Raman signals, Raman signal pattern recognition machine learning software, and a module and method for transmitting and receiving Raman signals to and from a server. Users of the device made by the present invention update optical signal data for each material on the server, enabling real-time update of signal patterns and libraries for each material, and users can share updated optical signal patterns and related models have.
The present invention provides a Ramcell and a Ramcell substrate, and a module and operating method using the same, including Surface Plasmonic Resonance (SPR), Polymerase Chain Reaction (PCR), and Enzyme-Linked Immunosorbent. /Immunospecific Assay, aka ELISA).
The present invention can be used as equipment, parts, and materials for drug analysis required for disease diagnosis and pharmaceuticals, and other various material analysis. The RPU of the present invention can be used for skin regeneration treatment, image extraction of internal organs, nutritional analysis of food, and the like. Through the present invention, the state of the body can be determined and predicted through analysis of the material of the body. It also allows us to judge the correlation between the material of the body and the psychological, racial, gender, social, economic, and geographical factors related to the subject of the body. Through the present invention, it is possible to quickly extract the optical signals of most materials included in the sample, so that the composition and characteristics of the sample can be measured as accurately and quickly as possible. Therefore, it can be easy to find and analyze trace substances. And the present invention is a platform that allows big data collection of material data, model optimization through it, and sharing of such big data and models.

Description

The platform that rapidly and accurately generates big data of optical signals for material analyzes and enables pattern recognitions, storage, and sharing of such data}

The present invention relates to the design, manufacture and arrangement of a substrate including a micro-sized cell (the inventor refers to such a cell as a Ramcell), which enables accurate and rapid extraction of Raman signals or SPR signals of materials in a sample for analysis, and Ramcell. platform and method, including a sample purification, processing and distribution module for analysis and an optical module for Raman signal extraction, a library storing Raman signal patterns, and matching and matching of Raman signal patterns and libraries extracted from Ramcell It is about a machine learning program for recognizing new patterns, a library and a server that can store new patterns, and related transmission and reception systems. This makes it possible to measure the composition of the substances contained in the sample as accurately and quickly as possible. Therefore, it can be easy to find and analyze trace substances.

Since the initial discovery of the Raman signal, various techniques have been developed to overcome the fine signal of the Raman signal. The surface-enhanced Raman Scattering (SERS) technology, which is a representative technology for signal amplification of Raman signals, is mostly plasmonic signal amplification by hot spots using metal substrates or metal nanoparticles. And there are many difficulties in using it as an actual diagnostic kit. For this reason, most of the devices using techniques such as PCR or ELIZA are used to determine the presence of disease or to efficiently detect drugs. However, in the case of PCR or ELIZA, there is a disadvantage that the method is difficult for the general public and the analysis time is long. In addition, PCR or ELISA is a method of detecting the presence of a specific target substance, and the type of substance to be detected is determined. SERS, which allows us to understand the structure of molecules through changes in the molecular frequency by near-infrared, visible, and ultraviolet, extracts various substances from the sample for analysis at once, and despite the fact that the pre-treatment process is rather simple, it has many advantages. There is a limit to its use in diagnostic devices for pharmaceuticals or drug detection devices for pharmaceuticals.

Most of the existing methods for enhancing the Raman signal intensity are to apply metal nanoparticles on a metal substrate or to position them in various ways. In this way, there is a problem in extracting a consistent Raman signal for the same material. First, the relative shape and size of metal nanoparticles for Raman signal amplification, and the relative position deviations between metal nanoparticles, between molecules in the sample for analysis, and between metal nanoparticles and molecules in the sample for analysis, within the same system and in each experiment The absence of a substrate system for amplification, which should be a standard, exists between systems applied to . For this reason, when the Raman signal of the same type of sample is extracted every time with the existing SERS system, the reliability of the SERS decreases somewhat due to the change in the frequency and intensity of each peak of the spectrum. The lack of reproducibility of the Raman signal between experiments is one of the main reasons why it is difficult to apply SERS as a medical diagnostic kit.

Another reason that it is difficult to extract a reliable Raman signal is the change in the Raman pattern due to the change in the composition of the material in the laser beam region due to the diffusion action of polymers and nanoparticles in the sample for analysis and the change in the bio sample due to the absorption of light by metal nanoparticles. etc. Moreover, it is difficult to separate the spectrum of a material having a similar frequency, and when the biomarker or material to be found is traced compared to other materials, the Raman signal of the target material is weak, so it is often hidden because it is buried in the spectrum.

In addition, when there are many substances in the sample for analysis, their Raman signals interfere with each other to form a spectrum that is difficult to interpret with the eye, and many AI techniques have been applied to overcome this interpretation. Separation of each Raman signal is very difficult due to the coexistence of substances with a relatively weak signal and a similar frequency to the relatively weak signals of numerous types of trace polymers and nanoparticles in the desired sample. In addition, there are many attempts to recognize the Raman signal pattern of blood plasma for early cancer diagnosis, but the ability to accurately discriminate is reduced due to the presence of the same marker of other cancers. Therefore, there are limitations with existing technologies due to early diagnosis. In addition, the presence and type of viral or bacterial infection can also be determined by changing the concentration of markers in the blood, but this can only be known when the infection progresses to some extent. As an example, the symptoms of coronavirus infection appear about two weeks after the initial infection, which means that the change in blood markers is measured by changes in hormones and immune system responses after the virus propagates to some extent. Therefore, it is at the level that directly determines whether the virus exists in the human body by PCR. Therefore, in order to use Raman for early diagnosis, technology that can determine the presence or absence of trace amounts of cancer, bacteria, and viruses must be supported.

There is also the issue of accessibility. The price and method of use of the equipment required to extract the existing Raman signal is difficult for the general public to access. At present, Raman spectroscopy is useful only to some experts, and it is difficult to commercialize it.

The absence of a Raman signal with high reproducibility and accuracy and the absence of a Raman signal that can be a reference is also a problem due to the various types of SERS chips and optical devices.

In order to solve the above problem, the present inventors provide a technology for designing, manufacturing and arranging a cell with a micro or larger size that can increase the reproducibility, sensitivity, and specificity of the Raman and SPR signals of the analyte material, aka Ramcell it is to do

Another object of the present invention is to provide an apparatus and method for processing, purifying, and dispensing an analyte to be located in Ramsell.

Another object of the present invention is to provide an apparatus and method that enable rapid optical signal extraction of materials located in Ramsel.

Another object of the present invention is to provide a library storing optical signals extracted from Ramsell, an optical signal pattern recognition machine learning program, a server for storing optical signals, and a related transmission/reception system and method.

Another object of the present invention is to provide a platform that helps general users to determine the composition of substances for self-diagnosis and analysis.

In order to achieve the above object, the present invention provides a method for characterizing, designing and manufacturing a substrate comprising a Ramcell.

The size of the Ramcell of the present invention is determined in consideration of the size of the material inside the sample to be analyzed. However, it must be above the minimum laser wavelength applied to extract Raman or SPR signals (also called optical signals). Therefore, the minimum size of Ramcell should be the maximum value among the applied laser wavelength and the size of the analysis target material inside the sample. The size of the Ramcell should be designed to minimize the increase in the temperature of the material in the Ramcell by the laser and to extract the spectrum of all materials as much as possible in the sample in the Ramcell.

As for the number of Ramcells, as the number of trace target substances to be measured is greater than the number of traces in the sample, there is a high possibility that the Raman signal of the target substance is clearly extracted.

If the average volume of solution occupied by one Ramsel A molecule is 1 mL and the average volume of solution occupied by one B molecule is 0.0001 mL, on average, there is one A molecule and 10,000 B molecules per 1 mL of Ramcell. Therefore, when the volume of the Ramcell is less than 1 mL, the number of B molecules present in the Ramcell including even one A molecule is less than 10,000 on average. Therefore, the Raman signal of the A molecule may be more pronounced compared to the Raman signal of the B molecule in the Ramcell of less than 1 mL than the Ramcell with a volume of 1 mL or more or the initial sample. In the extreme, if all the substances in the sample are similar in size and the volume of each Ramcell is very small, so that there is on average about one molecule per Ramcell, the measurement accuracy of all kinds and amounts of molecules in the sample can be very high.

Depending on how molecules are positioned on the plasmonic surface and how they receive light, the Raman spectrum may be different. Therefore, it is included in the present invention to extract the Raman spectrum for each material through light of various wavelengths and directions in a standardized Ramcell and form a library.

Also, since the concentration of the substance is related to the intensity of the Raman signal, the concentration of the substance can be inversely estimated through the spectrum extracted from Ramcells. Unlike general Raman signal extraction, the intensity of the Raman signal obtained using SERS may simply not be proportional to the concentration of the material. Therefore, it is necessary to extract the Raman spectrum by varying the amount of each material in the standardized Ramcell and form a library.

If the volume of Ramcell is reduced, the plasmon enhancement effect that each material receives can be increased. The present invention includes utilizing nanoparticles, electromagnetic fields, and light based on various types of materials to enhance weak signals.

In addition, since the magnitude of the signal corresponding to anti-stokes in the Raman spectrum tends to increase relatively as the temperature increases, it is possible to estimate the sample temperature inversely. The Raman spectrum according to each temperature should be extracted and libraryd.

The material and internal nanoparticles of the Ramcell of the present invention are configured to be capable of amplifying the optical signal intensity by a laser applied in consideration of the rotation direction and incident angle of the laser. Ramsel can form embossed or engraved nanoparticles according to the characteristics of the sample and the purpose of analysis. It also includes the use of materials such as semiconductors or graphene, or modules such as coolers, that can lower the temperature rise by hotspots caused by nanoparticles.

It includes exposure, etching, deposition, cleaning equipment and operation used in a semiconductor process to rapidly mass-produce a substrate including a standardized Ramcell of the present invention, and materials and components for using such equipment. In addition, 3D printers and various molding technologies that can engrave shapes on the substrate are also included.

The present invention includes a module and an operating method for rapidly extracting optical signals from a sample for analysis in a Ramcell. In order to extract the spectrum of all Ramcells most quickly, a micro-sized module including a laser, lens, spectrometer or TERS corresponding to each Ramcell that can extract Raman signals from each Ramcell is included. Configuration and arrangement of micro-sized modules including lasers, lenses, spectrometers, or TERS to cope with as many Ramcells as possible when it is not possible to have a module with a size suitable for each cell or there are modules that can respond to multiple Ramcells including this being done. It includes an operation method and module arrangement optimized to extract Raman signals as quickly as possible by extracting Raman signals from all Ramcells step by step or successively by the relative movement of the module or the substrate including the Ramcell.

The sample for analysis distributed to the Ramcell of the present invention includes a method and module that can be processed or purified before distribution in order to be efficiently distributed to the Ramcell. In one embodiment, the material can be purified by the size of the filter module and can be efficiently distributed by modules such as micro nozzles and micro fluidics. Various diamagnetism and paramagnetism combined with specific substances such as nucleic acids, antibodies, antigens, such as DNA/RNA combined with optical signal enhancing materials such as fluorescent materials and Raman signal enhancing materials through a diamagnetic, paramagnetic, and ferromagnetic structure and a mixer , It includes a module and operation method for creating a mixture containing a structure with ferromagnetic magnetism so that a magnetic material is present in the vicinity of the Ramcell or by generating an electromagnetic field in the Ramcell to place the magnetic material in the Ramcell.

It includes a machine learning program that matches the pattern and finds a new pattern by comparing the pattern of the optical signal extracted from the Ramcell of the present invention with a library storing various optical signals, a server for mass storage of optical signals, and a related transmission/reception system do. The updated optical signal and related model can be shared among users of the present invention through the server.

Through a platform including a module that can accurately and quickly extract Raman or SPR signals of substances in a sample for analysis of the present invention, relevant spectra can be extracted for most substances, including trace substances, in a sample for analysis. This makes it possible to quickly and accurately measure the types and amounts of trace substances and other substances in samples for analysis. One example where this can be applied is the early diagnosis of each disease.

1 is a flowchart showing the operation method of the integrated Raman signal analysis platform of the present invention.
2 is about the configuration of a substrate including a Ramcell. It is a perspective view showing the size, design, arrangement, and nanoparticles of Ramcell.
FIG. 3 shows that Ramcell and nanoparticles can be formed in various shapes including embossing or engraving by semiconductor methods or other microprocesses including 3D printers and moldings.
4 is a perspective view showing the configuration and arrangement of one type of module for simultaneously extracting Raman signals from multiple Ramcells.
5 is a perspective view showing the arrangement and operating principle of a module including an optical lens and a spectrometer.
6(a) to 6(c) are perspective views showing the components and operating principle of a module including an optical lens and a spectrometer. 6D is a perspective view showing the components and operating principle of a module including an optical lens and a spectrometer.
6(e) to 6(g) are perspective views showing the components and operating principle of the module including the TERS, the optical lens, and the spectrometer.
6(h) is a perspective view showing the components and operating principle of the module including the Ramcell including the TERS module and the optical lens and spectrometer.
6(i) to 6k are perspective views illustrating the components and operating principle of a module including an optical lens and a spectrometer in the case of a space containing an analyte in the photodetector.
7(a) is a perspective view of simultaneously extracting Raman signals from all Ramcells on a Ramcell substrate in which the size or method of the Raman spectrometer, TERS module, or laser module is, and 7(b) is the size of the Raman spectrometer, TERS module, or laser module. It is a perspective view of a method for extracting Raman signals by moving each module or Ramsel substrate when the method B fails to extract Raman signals from all Ramcells of the Ramsel substrate at the same time.
8( a ) is a perspective view illustrating a method of purifying a sample for analysis through a micro or nano size filter module and distributing a sample for analysis to each Ramcell through a micro or nano size nozzle.
8 (b) is a perspective view of a method of purifying a sample for analysis through a micro or nano size filter module and distributing the sample for analysis to Ramcell through a micro-fluidic system.
FIG. 8(c) is a perspective view illustrating a method in which a micro- or nano-sized tip pipette is positioned above each Ramcell, and a sample for analysis is positioned in a Ramcell region with a micro- or nano-size controller.
8( d ) is a perspective view illustrating a method in which a flexible micro- or nano-sized tip pipette moves to each Ramcell and places a sample for analysis in the Ramcell region.
FIG. 8(e) shows that a sample for analysis is purified through a micro or nano size filter module, and magnetic particles are detected because parts or regions containing diamagnetic, paramagnetic, or ferromagnetic materials or generating a magnetic field exist in or near Ramcell. It is a perspective view of how it can be collected. When various diamagnetic, paramagnetic and ferromagnetic substances are gathered in Ramcell, non-magnetic substances that are not gathered in Ramcell can be removed with a cleaning solution.
8(f) shows that the sample for analysis is placed on the Ramcell substrate through the sample inlet tube, the sample is dispersed over the entire area of the Ramcell substrate through the rotator, and parts or regions containing diamagnetic, paramagnetic, ferromagnetic materials or generating a magnetic field It is a perspective view of a method that can collect magnetic particles that exist in or near Ramsel.
9 is a perspective view of sending a module including a prism or various spectrometers for SPR located under each Ramcell and a module 290 including a light receiver from a prism or a spectrometer to receive and reflect light 270 from a light source for SPR.
10 is a perspective view showing the arrangement and operating principle of modules including a module including a prism or various spectrometers for SPR, a light source for SPR, and a light receiver from a prism or a spectrometer when viewed from under a Ramsel substrate.
11 (a) is a perspective view showing the components and operating principle of a module including a light receiver and a light source for SPR from a prism or a spectrometer, and a module including a prism or various spectrometers for SPR. (b) is a perspective view showing the components and operating principle of a module including a light receiver module from a prism or spectrometer, a module including a light source for SPR, and a module including a prism or various spectrometers for SPR. (c) is a perspective view showing the module components and operation principle including the light receiver from the prism or spectrometer, the light source for SPR, and the prism or various spectrometers for SPR.
12 shows the effect of isolating a complex Raman signal that may be generated by a large number of molecules in a sample for analysis before being distributed to each Ramcell through the Ramcell. Although this figure uses a Raman signal as an example, there is an effect that the SPR signal, Raman image, or image can also be separated through each Ramcell.
13 is a process through the process of FIG. 1 , including a process of extracting a sample from a Ramcell determined to have a verified target signal through the process of FIG. 1 and mixing it with a solution in an amount that can be put back into all Ramcells on a Ramsel substrate is a perspective view showing This process may be repeated to satisfy the user's desired separation of the Raman spectrum.
14 is a perspective view illustrating a process of comparing and matching a spectrum extracted from each Ramcell with a spectrum of a reference material. The spectrum in the figure is a Raman spectrum as an example, but various signals such as an SPR signal can be applied.
15 is an analysis platform device or component according to any one of claims 1 to 24 made using, in part or integrally, the technology of the claims within each claim.
17 is a perspective view illustrating a method for Ramsell to extract a Raman signal for a trace material.
18 is a perspective view of a module for concentrating factors that cause internal respiratory diseases or infections in water or other solutions through exhalation.
19 is a perspective view illustrating a movement path pattern of a beam in a Ramsell.
20 is a perspective view of components and an operating principle of a RamCell Processing Unit (aka, RPU).
21 is a view showing big data extraction for each pure substance and mixed substance, design optimization of Ramcell and Ramcell substrate, model test, sample material analysis and diagnosis, optical signal big data library according to claims 1 to 24 of this patent It is a flow chart for model update and a suggested diagram showing the big data extraction, pattern recognition, storage, and sharing module and operation method of the material analysis platform of this patent.
22 is a perspective view of the configuration and method of the module according to claim 20 and 26 of the present patent, wherein the RPU extracts an optical signal using an optical filter.
23 is a perspective view of a module and method for moving the substrate 880 including the RPU and moving the RPU within the substrate.
24 is a perspective view showing the components of the RPU.
25 is a perspective view showing a system composed of one diffraction foot among the spectrometer systems for extracting optical signals from each Ramcell simultaneously or for each time.
26 is a perspective view of the configuration and operation method of a portable material analysis platform device that can be made using the optical signal extraction module and material distribution module of the present patent, and a Ramcell substrate or a SERS substrate.
27 (a) is a perspective view of a specific structure capable of collecting specific substances of an analyte sample. It is a perspective view of a substance that binds to a substance in an analysis sample and a structure with or without diamagnetic, paramagnetic, or ferromagnetic magnetism applied to the surface. The shape in the perspective view can vary widely depending on the bonding material and structure. (b) is a perspective view showing the binding between the target material in the analyte sample, a material binding to them, and a material including a fluorescence or Raman signal enhancing material that enhances the optical signal of the target material. (c) indicates that the target material in the analysis sample, a material containing a fluorescent or Raman signal enhancing material that enhances the optical signal of the target material, or a material binding to the target material has diamagnetic, paramagnetic, or ferromagnetic magnetism applied to the surface It is a perspective view showing the coupling between the structures that have not been done.
28 is a perspective view of a process of detecting a trace amount of a target material through the diamagnetic, paramagnetic, and ferromagnetic magnetic structure and mixer of claim 5, the optical signal extraction module of claims 8 and 26, and the electromagnetic generation module of claim 13 to be. The shape and number of each substance in the schematic varies.
Figure 28 (a) shows a substance that binds to a substance in an analysis sample, a structure having diamagnetic, paramagnetic, and ferromagnetic magnetism applied to the surface thereof, and a substance including the type of nucleic acid, protein, etc. to be detected by the structure. It is a perspective view of a material combined with a material 1080 including a fluorescence or Raman signal enhancing material that enhances the optical signal of the target material and the target material.
Figure 28 (b) shows an optical signal enhancing material such as a fluorescent material and a Raman signal enhancing material in the analysis sample, and a specific material such as a nucleic acid such as DNA/RNA that binds or does not bind to them, an antibody, and an antigen, and a material that binds them A mixture of various diamagnetic, paramagnetic, and ferromagnetic magnetic structures applied to the surface is mixed with optical signal enhancing materials such as fluorescent materials and Raman signal enhancing materials in the analysis sample through a material reactor or mixer, and DNA/RNA combined with them It is a perspective view of the formation process of a mixture including various diamagnetic, paramagnetic, and ferromagnetic structures bound to specific substances such as nucleic acids, antibodies, and antigens.
28(c) shows various diamagnetic, paramagnetic, and ferromagnetic magnetisms combined with specific substances such as nucleic acids, antibodies, and antigens such as DNA/RNA combined with optical signal enhancing materials such as 28(b) fluorescent materials and Raman signal enhancing materials. The band is a perspective view of the process in which the mixture including the structure is put into the module of FIG. 8(f).
FIG. 28( d ) is a perspective view illustrating a process in which the mixture in the module of FIG. 8( f ) of FIG. 28( c ) is evenly distributed on the Ramsel substrate through the rotator 690 .
FIG. 28(e) is a perspective view illustrating a process in which a magnetic material is present near a Ramcell or an electromagnetic field is generated in the Ramcell to place the magnetic material in the Ramcell.
FIG. 28(f) is a perspective view illustrating a process of removing materials other than those located in the Ramsell through magnetism through the cleaning solution 1110. Referring to FIG.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. Since the present invention may have various changes and may have various forms, only specific embodiments will be described in detail. However, this is not intended to limit the present invention to the specific disclosed form, it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention.

1 is an operation flowchart of the Raman signal platform of the present invention.

Referring to FIG. 1 , first, a sample for analysis may be obtained and purified. There are very various techniques for the purification method in consideration of the difference in physical and chemical properties between substances. For example, to extract the Raman signal of a virus or a related substance to measure the presence and concentration of a related virus in the blood of a person suspected of having hepatitis B virus infection, first collect the blood, and then separate the plasma solution with a centrifuge. can Additionally, a filter module for removing substances having a specific size or larger may be used as shown in FIG. 8 . For example, in order to filter out substances larger than 1 μm in the extracted plasma solution, a filter module with pores of less than 1 μm in size may be used. A module for extracting the Raman signal, acquiring and purifying the target sample is part of the platform of the present invention.

Sample processing for analysis is a process for correctly dispensing the Ramsel of the present invention. The efficiency of distribution can be improved by changing the chemical properties of the sample for analysis. For example, in the case of a sample for analysis with high viscosity, a solution to lower the viscosity may be added, and the viscosity may be lowered by increasing the temperature to a level that does not cause destruction of the material in the sample. Also, conversely, when a low-viscosity material is dispensed in an inkjet format, the viscosity and adhesion to the Ramsel surface can be increased. A drop of blood can be diluted in water. When the concentration of the initial cancer biomarker is 10 ^-12 M, the volume occupied by the biomarker is about 1661 μm3. Since the volume of one drop of blood is about 20 μL, about 12x10 ⁶ biomarkers can exist in one drop. Therefore, by sufficiently diluting in water, it is possible to sufficiently extract optical signals related to cancer biomarkers using one or more Ramsel substrates.

The sample dispensing process may be a dispensing process by a module for sample dispensing or a simple artificial dispensing process. For example, as in FIG. 8 , it may be a case of dispensing by a nozzle or a microfluidic system, or a case in which a sample contained in a container is sprayed and dispensed by a user's hand.

Spectrum extraction is a process accompanied by a module and operation for spectrum extraction as shown in FIGS. 6 and 7 .

Spectral analysis is a visual analysis that judges composition through a spectrum, an analysis process through a program with or without AI technology.

2 is about the configuration of a substrate including a Ramcell. It is a perspective view showing the size, design, arrangement, and nanoparticles in the Ramcell 10 .

The size of the Ramcell of the present invention is determined in consideration of the size of the material inside the sample to be analyzed. However, it must be at least 1 μm to extract the Raman signal. Therefore, the size of Ramcell should be the maximum value between 1 μm and the size of the analyte material inside the sample. For example, when a sample of blood is to be distributed in a ramcell to determine the presence of harmful bacteria in the blood, the size of the ramcell must be at least 1 μm, but larger than the size of the bacterium. Since most bacteria have a size of 0.2 μm to 2 μm, the size of Ramcell must be at least 2 μm for the detection of all possible blood bacteria. And, there is no limit to the maximum size of the Ramcell, but as described above, it should be designed in consideration of the temperature rise of the sample and efficient sample spectral extraction.

In the case of an early bacterial infection, the blood level of the bacteria can be as low as 1 CFU/mL. For bacteria to enter at least one Ramcell, more than 10000 Ramcells would be required for 0.0001 mL per Ramcell, assuming that the undiluted sample blood is distributed into all Ramcells. However, undiluted blood samples produce strong fluorescence, which interferes with Raman spectral extraction. Therefore, dilution may be required or a Raman spectrometer with a long wavelength may be required. Therefore, in case of dilution, if there are 10000 Ramcell substrates per one Ramcell substrate, more than one Ramcell substrate will be required.

The shape of the substrate including the Ramcell of FIG. 2 may vary depending on the shape of the platform desired by the user, such as a square ( FIG. 2A ) and a circular shape ( FIG. 2B ). In addition, the shape of the Ramcell can also be varied for the characteristics of the sample distributed to the Ramcell and for efficient Raman signal extraction. A position marker 400 for locating and adjusting a position is positioned on the substrate of FIG. 2 . This position marker can be used by various types of sensors to accurately locate the substrate, and can be designed and positioned according to the type and sensitivity of the sensor and various purposes. As the size of the substrate increases, the height of each portion of the substrate may be different compared to other regions. Therefore, a position marker capable of measuring the height of the substrate may be positioned inside the substrate.

3 is a perspective view showing the configuration of the nanoparticles 20 in the Ramcell 10 through various exposure, deposition, and etching methods.

3 shows that the Ramcell 10 and the nanoparticles 20 can be configured in various shapes including embossing or engraving by a semiconductor method or other microprocesses including 3D printers and moldings.

The structure and nanoparticles of the Ramcell of the present invention can be designed in consideration of the polarization direction and the incident angle of the laser. For example, considering the incident angle of the laser, the Ramcell should be designed so that the laser penetrates the material inside the Ramcell. Materials and nanopatterns to amplify the Raman signal strength inside the Ramcell are very diverse. The middle region 410 between the Ramcells located closest to each other and the edge of the Ramcell 10 may coincide. In this case, Ramcells located closest to each other of the Ramsel substrate may be in contact with each other, so that only the Ramcell may exist in the Ramsel substrate. The surface 420 of the Ramcell may be made of various materials. For example, it may be coated with a hydrophilic, hydrophobic material. In addition, it may be applied with materials such as antibodies, antigens, and aptomers. The Raman signal or SPR signal generated by the binding of an antibody to an antigen or aptomer can give important clues to determining whether pathogens or antibodies are formed in bodily fluids, and effective drug extraction. Ramsel, the size, shape, number, arrangement, etc. of the internal nanoparticles shown in FIG. 3, and the like, a material for surface treatment, etc. can be formed in various forms by those of ordinary skill in the art without departing from the technical spirit of the present invention. Substitutions, modifications, and alterations may be made and are also within the scope of the present invention.

Figure 3 (a) is a schematic view showing that the shape of the ram cell can be designed in various ways. It should be designed for efficient optical signal extraction.

3(b) is a schematic diagram showing that nanoparticles in Ramcell can be designed in various ways. It should be designed for efficient optical signal augmentation.

4 is a perspective view showing the configuration and arrangement of one type of module for simultaneously extracting Raman signals from multiple Ramcells.

Figure 4 (a) is a monochromator type optical system. A module 70 including a lens 80 , a grating 90 , and a CCD/CMOS 100 positioned on each Ramcell receives the laser 60 emitted from the laser device 50 , and extracts the Raman signal of the analyte in each Ramcell. It is a perspective view showing what In FIG. 4 , there is a module 70 including three Raman spectrometers, but as many modules as the number of all Ramcells on one side are arranged side by side, it is possible to extract Raman signals of all one Ramcell at the same time. If the size of the module is larger than that of the Ramcell, one module may extract Raman signals of several Ramcells, or the module or the substrate including the Ramcell may move to extract Raman signals. In addition to the Czerny Turner monochromator type, various types of monochromator are possible. For Raman imaging, the module 70 including a Raman spectrometer may include various types of imagers including a CMOS camera.

4(b) is an optical system based on an interferometer. The light scattered from the analysis sample is separated through the beam splitter 750 and reflected on the fixed mirror 710 and the moving mirror 720, respectively, and then combined again to calculate the spectrum through the FT detector using the intensity of the interfered beam becomes this

Fig. 4(c) is an optical system using a transmission diffraction foot. The shape of the transmission diffraction grating may be various, such as Volume Phase Holography Diffraction Grating (aka, VPH diffraction grating) or Digital Planar Holography Diffraction Grating (aka, DPH diffraction grating).

5 is a perspective view showing the arrangement and operating principle of a module including a laser module, a laser reflector, an optical lens, and a spectrometer.

FIG. 5 includes a top-down view of the state of FIG. 4 and a state in which a laser is delivered to a module through a laser reflector on each Ramsel. In Fig. 5, there is a module 70 comprising a Raman signal extraction device such as 5 reflectors and 5 Raman spectrometers corresponding to each reflector, but the number of reflectors as many as all the Ramsels on one side is arranged side by side, so that all one at a time at a time It is possible to extract the Raman signal of Ramsel. If the size of the reflector is larger than that of the Ramcell, one reflector may simultaneously extract the Raman signals of several Ramcells, or the module including the reflector and the Raman spectrometer or the substrate including the Ramcell may move to extract the Raman signals. Since the number and position of the reflector and the Raman signal extraction module can be very diverse, the size, shape, number, arrangement, etc. of the modules shown in FIG. 5 are common knowledge in the art without departing from the technical spirit of the present invention. Substitution, modification and change of various forms will be possible by those having, this also falls within the scope of the present invention.

6(a) to 6(c) are perspective views showing the components and operating principle of a module including an optical lens and a spectrometer. This module may contain a part of the RPU, or may be replaced by an RPU.

According to FIG. 6( a ), a substrate or material through which a laser or other types of light passes is positioned under the Ramcell, and a module including a laser diode or a micro LED is positioned under it. Above the Ramsel is placed the module containing the optical lens and the spectrometer (the grating and the CCD receiver). Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.

According to FIG. 6(b), a module including a laser diode or a micro LED is positioned under the Ramcell. Above the Ramsel is placed the module containing the optical lens and the spectrometer (the grating and the CCD receiver). This module may contain a part of the RPU, or may be replaced by an RPU. According to FIG. 6( c ), a module including a laser diode or a micro LED is positioned under the Ramcell. Modules including optical lenses and spectrometers (lattice and CCD receiver), lasers for SERS, and various light sources are located on Ramsell. Ramsell and lenses can come into contact.

Figure 6 (d) is a perspective view showing the components and operating principle of the module including the optical lens and the spectrometer. This module may contain a part of the RPU, or may be replaced by an RPU. The spectrometer including the CCD can be replaced with an FT Raman detector and related modules. There may be a material through which light passes between the laser and the substrate.

6(e) to 6(g) are perspective views showing the components and operating principle of the module including the TERS, the optical lens, and the spectrometer. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.

According to FIG. 6(e), the TERS module 350 including the TERS signal receiving system is located on the Ramsel. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.

According to FIG. 6(f), a module 340 including an optical lens, a spectrometer (a grating and a CCD receiver), a laser diode or a micro LED, and a TERS module 150 without a TERS signal receiving system are located on the Ramcell. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.

According to FIG. 6( g ), a module including an optical lens and a spectrometer (a grating and a CCD receiver), and a Tip Enhanced Raman Spectroscopy (TERS) module are positioned on the Ramsel. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU. A module containing a laser diode or micro LED is located under the Ramsel.

6(h) is a perspective view showing the components and operating principle of the module including the Ramcell including the TERS module and the optical lens and spectrometer. A module 340 including an optical lens, a spectrometer (a grating and a CCD receiver) and a laser diode or micro LED is positioned on the Ramsel. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.

In FIG. 6(i), the photodetector 70 has a space for storing the analyte, and there is an optical signal amplifying substrate at the top. Therefore, the photodetector acts as a Ramsel. There is a lens through which the laser passes on the upper part of the substrate, and the light emitter 140 is present on the upper part of the lens.

In FIG. 6( j ), the photodetector 70 has a space for storing the analyte, and there is an optical signal amplifying substrate at the top. Therefore, the photodetector acts as a Ramsel. A light emitter 140 is provided on the top of the substrate.

In FIG. 6(k) , the photodetector 70 has a space for storing the analyte, and there is an optical signal amplifying substrate at the top. Therefore, the photodetector acts as a Ramsel.

7(a) is a perspective view of the Raman spectrometer, TERS module, and the size or method of the laser module simultaneously extracting Raman signals from all Ramcells on the Ramcell substrate, and 7(b) is the size or method of the Raman spectrometer, TERS module, or laser module. It is a perspective view of a method of extracting a Raman signal by moving each module or a Ramcell substrate when it is impossible to simultaneously extract a Raman signal from all Ramcells of the Ramcell substrate due to a limitation of the method. Ramsell and lenses can come into contact. Each module includes a part of the RPU or can be replaced with an RPU. Similarly, SPR modules can extract SPR signals by moving relative to the Ramcell substrate.

8( a ) is a perspective view illustrating a method of purifying a sample for analysis through the micro or nano size filter module 160 and distributing the sample for analysis to each Ramcell through the micro or nano size nozzle 170 . For efficient purification, the filter inlet 180 may have a high pressure, and the outlet 210 may have a low pressure. High pressure can be achieved through compression or physical compression of the gas. However, it must be at the pressure and temperature that ensures the correct positioning of the analyte in the Ramsel.

8( b ) is a perspective view illustrating a method of purifying a sample for analysis through the micro or nano size filter module 160 , and distributing the sample for analysis to Ramcell through the micro-fluidic system 190 .

FIG. 8(c) is a perspective view illustrating a method in which a micro- or nano-sized tip pipette 360 is positioned above each Ramcell, and a micro- or nano-size controller 370 places a sample for analysis in a Ramcell region.

8( d ) is a perspective view illustrating a method in which a flexible micro- or nano-sized tip pipette 390 moves to each Ramcell while positioning a sample for analysis in the Ramcell region. The flexible micro or nano-sized tip pipette 390 module is equipped with an atomic force microscope (aka AFM) or various sensors so that when the tip is correctly positioned in each Ramcell area, the sample for analysis is placed in the Ramcell area. giving way is possible.

8(e) shows that a sample for analysis is purified through the micro or nano size filter module 160, and a component or region 1060 containing a diamagnetic, paramagnetic, or ferromagnetic material or generating a magnetic field exists in or near the Ramcell. This is a perspective view of a method that can collect magnetic particles. When various diamagnetic, paramagnetic, and ferromagnetic substances with a substance that bind to a specific substance in the analyte sample are applied to the surface of the analysis sample, the non-magnetic substances that are not collected in the Ramcell can be removed with a cleaning solution. An optical signal extraction module may be included or connected.

8(f) shows that a sample for analysis is placed on a Ramcell substrate through the sample input tube 660, the sample is dispersed over the entire area of the Ramcell substrate through a rotator 690, and contains a diamagnetic, paramagnetic, or ferromagnetic material or a magnetic field is applied. It is a perspective view of a way in which the generating part or region 1060 can collect magnetic particles by being present in or near the Ramsel. Non-magnetic substances that do not collect in the Ramsel can be removed with a cleaning solution. An optical signal extraction module may be included or connected.

9 shows a module 300 including a prism or various spectrometers for SPR located under each Ramsell, and a module 290 including a light receiver that receives light from a light source 280 for SPR and reflects light 270 from a prism or a spectrometer. ) is a perspective view sent to Although a module including a prism or various spectrometers is not visible in FIG. 9 , it can be seen that they are located under each Ramsell in FIG. 10 . 9 shows a module 290 including a light receiver from three prisms or spectrometers, but as many modules as the number of all Ramcells on one side are arranged side by side, it is possible to extract SPR signals of all one Ramcell at the same time. If the size of the module is larger than that of the Ramcell, one module can extract the SPR signal of several Ramcells, or the module or the substrate including the Ramcell can move to extract the SPR signal.

10 is a module 300 including a prism or various spectrometers for SPR, a light source 280 for SPR, and a module 290 including a light receiver from a prism or a spectrometer when viewed from under the Ramsel substrate. is a perspective view.

11 (a) is a perspective view showing the components and operating principle of the module 320 including a light receiver for SPR and a light source for SPR and a module 300 including a prism or various spectrometers for SPR or spectrometer. (b) is a perspective view showing the components and operating principle of a module 300 including a light receiver module 290 from a prism or a spectrometer, a module 280 including a light source for SPR, and a module 300 including a prism or various spectrometers for SPR. (c) is a perspective view showing the module components and operation principle including the light receiver from the prism or spectrometer, the light source for SPR, and the prism or various spectrometers for SPR.

12 shows the effect of isolating a complex Raman signal that may be generated by a large number of molecules in a sample for analysis before being distributed to each Ramcell through the Ramcell. Although this figure uses a Raman signal as an example, there is an effect that the SPR signal, Raman image, or image can also be separated through each Ramcell. In the figure on the left of FIG. 12 , there are 9 Raman signals of 9 molecules under the assumption that there are 9 molecules in the sample for analysis. If there are 1000 molecules, it will get even more complicated. It shows that one or two signals are extracted from each Ramcell as shown in the figure 440 on the right so that the nine Raman signals can be easily analyzed.

13 is a process through the process of FIG. 1 , including a process of extracting a sample from a Ramcell determined to have a verified target signal through the process of FIG. 1 and mixing it with a solution in an amount that can be put back into all Ramcells on a Ramsel substrate is a perspective view showing A magnetic material is placed in a Ramcell to which a magnetic field is applied or a magnetic material is located nearby, and after no magnetic field is applied or the magnetic material is moved away from the Ramcell, the magnetic materials that can move out of the Ramcell are collected and re-ramcelled. It can be distributed on the substrate. This process may be repeated to satisfy the user's desired separation of the Raman spectrum. PCR and ELISA can be performed in the Ramcell determined to have the target signal, or the sample in the Ramcell can be moved to the PCR and ELISA module for analysis.

14 is a perspective view illustrating a process of comparing and matching a spectrum 440 extracted from each Ramcell with a spectrum 450 of a reference material. The spectrum in the figure is a Raman spectrum as an example, but various signals such as an SPR signal can be applied.

The spectrum of the reference material in FIG. 14 is a library of spectra of each material already discovered or a spectrum of each newly discovered material, and is matched with the pattern of the spectrum extracted from each Ramcell, and the type and amount of the material in the sample for analysis can be analyzed. For matching, Principal Component Analysis (aka PCA), Partial Least Squares (PLS), Convolutional Neural Network (aka CNN), Support Vector Machine (aka SVM), etc. Various machine learning techniques can be utilized.

15 is an analysis platform device or component according to any one of claims 1 to 24 made using, in part or integrally, the technology of the claims within each claim.

Using the components of the instrument, it is possible to analyze the type and amount of substances in the sample for analysis of Ramsel.

16 is a mixer according to claim 5, wherein the material of the sample is evenly mixed and mixed.

It promotes the even mixing of substances and the reaction between substances through the mixer.

Figure 16 (a) is a perspective view showing a module for evenly mixing the sample through the impeller. The sample input tube 660 passes through the inside of the mixer to help materials to move into the mixer. The impeller 670 of the mixer may exist in various forms depending on the characteristics of the material to be mixed. For example, the material coming in from the top of the mixer may be blood extracted from a patient, and the material coming in from the bottom of the mixer may be a substance with nanometals that can bind to viruses or bacteria in the blood, or an antibody that binds fluorescence. have.

Figure 16 (b) is a perspective view showing a mixer in the form of mixing and mixing by rotating or shaking the rotator 690 in a state in which the holder 680 holds the container containing the sample.

17 is a perspective view illustrating a method for Ramsell to extract a Raman signal for a trace material.

17( a ) is a perspective view of a Raman spectrum with two A molecules and 20 B molecules present in the initial sample. It shows that the pick of molecule A is not visible.

17( b ) is a perspective view of a Raman spectrum when an initial sample is divided into two regions. It shows that the Raman spectral peaks of molecules A and B are both reduced.

17( c ) is a perspective view of a Raman spectrum when an initial sample is divided into three regions. The Raman signal of molecule A is more prominent.

18 is a perspective view of a module for concentrating factors that cause internal respiratory diseases or infections in water or other solutions through exhalation.

18 (a) is a module for extracting a sample by moving the opener 800 through the sample extraction tube when a factor of respiratory disease or infection is concentrated in water or other solution through the exhalation straw 760. The number and location of the sampling tubes may vary.

18( b ) is a module for extracting a sample by moving the opener 800 through the sample extraction tube when a factor of respiratory disease or infection is concentrated in water or other solution through the exhalation straw 760 . This module also has a structure in which only the sample container 780 can be removed after the material on the sample container is removed through the sample extraction tube 790 . The sample container may have various shapes. The number and location of the sampling tubes may vary.

19 is a perspective view illustrating a movement path pattern of a beam in a Ramsell.

19 (a) is a perspective view showing that the beam moves from the center in the Ramcell to the edge of the Ramcell in a whirlpool-shaped path, and then moves to the path coming back to the center from the edge. The starting and ending points and the path pattern size can be set by the user.

19( b ) is a perspective view showing that the beam moves from one side of the Ramsell in a zigzag manner and arrives at the other side in a zigzag manner again to the other side. The starting and ending points and the size of the path pattern can be determined by the user.

19( c ) is a perspective view showing that the beam rotates in the same pattern in the Ramsel. You can turn in the same direction and then in the opposite direction. The rotating pattern is available in circles, squares, and other geometric shapes. The starting and ending points and the size of the path pattern can be determined by the user.

20 is a perspective view of components and an operating principle of a RamCell Processing Unit (aka, RPU).

The light emitted through the light emitting module including the LED of the RPU enters the Ramcell region and the scattered light is received by the module including the photodetector such as CCD, and optically through the MAC, CPU, and SRAM, which are the core operators of transform and deep learning operations. It is a unit that converts a signal into a digital signal through AI techniques such as Fourier or Laplace transform and DNN. Here, the photodetector may include a reflection and transmission diffraction foot, a lens, and a reflection mirror of the present patent. Here, LED is a laser diode, CCD is CMOS, or other alternative technologies described in this patent can be changed. It is possible to install memory chips such as DRAM and NAND to store data libraries or models in the RPU.

21 is a view showing big data extraction for each pure substance and mixed substance, design optimization of Ramcell and Ramcell substrate, model test, sample material analysis and diagnosis, optical signal big data library according to claims 1 to 24 of this patent It is a flow chart for model update and a suggested diagram showing the big data extraction, pattern recognition, storage, and sharing module and operation method of the material analysis platform of this patent.

21(a) is a flowchart for big data extraction and optimization of Ramcell and Ramcell substrate design for each pure substance and mixed substance.

First, according to claims 1 to 4, a Ramcell and a Ramcell substrate are designed. And after processing the modeling sample according to claim 5, big data is extracted through the analysis platform of claim 18. A library is created based on the software and hardware of claims 19 and 22, and optical signal patterns representing each pure substance and mixture are modeled through the software of clause 20. And these libraries and models are stored in the platform or server of the 18th and 22nd paragraphs.

21 (b) is a flowchart for testing the model processed in 21 (a). Process the sample for model testing according to claim 5. After identifying the composition and characteristics of each pure substance and mixed substance in advance, the big date is extracted through the analysis platform of claim 18. The extracted big data is added to the library created based on the software and hardware of Articles 19 and 22 to update the existing library. Through the extracted big data, it is applied to the model made as shown in FIG. 21(a) to verify to what level the composition and characteristics of the test material can be grasped. If the model result is accurate to the level desired by the user, the existing model can be updated with the updated library and stored on the platform and server. If the accuracy of the model is low, the order of designing and optimizing the Ramcell and Ramcell substrate, processing the sample for modeling, or processing the model of FIG. 21(a) is returned.

21(c) is a flowchart of analyzing a sample for analysis through the model verified in 21(b) and performing early diagnosis. A sample for analysis is obtained and processed according to claim 5 . This applies to the analysis platform of claim 18. When applied, information may be entered into the analytics platform as in clause 23. Through the input information and samples for analysis, the analysis platform extracts big data. The extracted big data is added to the library made based on the software and hardware of paragraphs 19 and 22, updates the existing library, and is stored in the platform or server of paragraphs 18 and 22. By applying the extracted big data to the model verified in FIG. 21( b ), the analysis result is provided to the user through the module of claim 21 .

Figure 21 (d) is a perspective view showing the big data extraction, pattern recognition, storage, and sharing module of the material analysis platform of the present patent.

Figure 21 (e) is a perspective view showing an operating method of the material analysis platform of the present patent.

22 is a perspective view of the configuration and method of the module according to claim 20 and 26 of the present patent, wherein the RPU extracts an optical signal using an optical filter.

22( a ) is a perspective view showing an array of RPUs.

22B is a perspective view illustrating an optical filter array. An array 860 of elements capable of filtering EUV, NUV, NIR, MIR, FIR, and specific wavelengths of visible light (eg, RGB colors). Each color represents the type of filter that can accept each specific wavelength. An example in which seven filter elements are repeatedly arranged is given in the perspective view. However, the range of filterable wavelengths, the number of filter types, and the array configuration can be very different. Various substitutions, modifications, and changes will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention.

Figure 22 (c) is a perspective view showing one RPU element including an optical filter. The laser emitted through the exit 840 of the laser is scattered by the analyte and may pass through the module 85 composed of specific wavelength filter arrays.

Figure 22 (d) is a perspective view showing that the RPU is possible in various forms. This patent also includes forms other than those shown in the perspective view.

Figure 22 (e) is a perspective view showing the variety of the laser exit module and laser output method. In the figure on the left, the light emitted from the laser exit through the beam splitter is scattered, and the back scattering light is received and passed through the beam splitter to the rear end, and the right figure is the form without the beam splitter. A beam splitter can reflect light of a specific wavelength and pass a specific wavelength. The exit 840 of the laser may be composed of an element in which the wavelength of the light that can be transmitted in the exit direction and the incoming direction is the same or different.

23 is a perspective view of a module and method for moving the substrate 880 including the RPU and moving the RPU within the substrate.

In the substrate 880 including the RPU, the RPU is capable of fine movement 910 up, down, left, and right relative to the substrate plane, and fine movement 910 up and down for confocal depth aiming. Rotation 920 is also possible to allow for an accurate angle of incidence. In order to change the position of the substrate including the RPU, the rotation 920 between the RPU substrate and the length adjustment module 890 connected to it is possible. Rotation is possible in the up, down, left, and right directions between the length adjustment modules connected to each other.

24 is a perspective view showing the components of the RPU.

The RPU is a processing unit including at least one of a module 970 for processing optical signal data generated after simultaneously extracting optical signals of several Ramcells in parallel or a module 950 for transmitting and receiving data.

24 is a module 980 including a light emitter or a light emitter, a data processing module 970 for interpreting or changing optical signal data, a module 960 for storing memory data such as an optical signal library or other non-memory data; And it is a perspective view showing the RPU composed of a module 950 for transmitting and receiving data.

25 is a perspective view showing a system composed of one diffraction foot among the spectrometer systems for extracting optical signals from each Ramcell simultaneously or for each time.

25 (a) shows that the light emitter located at the top of each Ramcell 940 emits a laser to the analysis sample of the Ramcell, and the scattered light passes through the beam splitter and the lens module 940 into the module including the reflective diffraction foot and the reflective mirror, It is a perspective view of a method in which light is diffusely diffracted by a single reflective diffraction beam through parallel reflective mirrors that reflect light scattered from each Ramcell, and enters a photodetector configured in parallel by reflective mirrors configured in parallel.

25 (b) shows that the light emitter located at the top of each Ramcell 940 is applied to the analysis sample of the Ramcell for a specific time.

The scattered light by shooting a laser is sent to the module including the reflective diffraction foot and the reflective mirror by the beam collector and path converter (including the lens/mirror) through the beam splitter and the lens module 940, and is reflected as one through the reflective mirror. It is a perspective view of a method of being diffusely diffracted by the diffraction foot and then entering the photodetector by the reflective mirror.

26 is a perspective view of the configuration and operation method of a portable material analysis platform device that can be made using the optical signal extraction module and material distribution module of the present patent, and a Ramcell substrate or a SERS substrate.

The optical signal extraction module 500 , the module including the Ramsel substrate 460 or the SERS substrate 1020 that does not contain a material, and the material distribution module 490 are all combined and can be carried as a single device. Modules including the optical signal extraction module 500 , the Ramsel substrate 460 , or the SERS substrate 1020 may be connected to each other by a connecting shaft, and may be unfolded during material analysis. For the material analysis module, place the sample into the sample inlet of the material dispensing module. When the optical signal extraction module includes a container containing a substance, the substance dispensing module is attached to the optical signal extraction module to dispense the substance. And after attaching the module including the SERS substrate on the optical signal extraction module, material analysis is performed. When the optical signal extraction module does not have a container for containing the material, the material is dispensed by attaching the material dispensing module to the module including the Ramsel substrate. Then, after attaching the optical signal extraction module on the module including the Ramcell substrate, material analysis is performed.

27( a ) is a perspective view of a specific structure capable of collecting specific substances of an analyte sample. It is a perspective view of the material 1040 binding to the material in the analyte sample and the structure 1050 with or without diamagnetic, paramagnetic, or ferromagnetic magnetism applied to the surface thereof. The shape in the perspective view can vary widely depending on the bonding material and structure.

27 (b) shows a substance 1040 binding to a substance in an analysis sample, a substance including a nucleic acid, a protein, etc. to be detected, a target substance 1070 to be detected, and a fluorescence enhancing optical signal of the target substance. It is a perspective view showing the coupling between the materials 1080 including the Raman signal enhancement material.

FIG. 27(c) shows a substance 1040 binding to a substance in an analysis sample, a substance including a nucleic acid, a protein, etc. to be detected, a target substance 1070 to be detected, and a fluorescence enhancing optical signal of the target substance. A material including a Raman signal enhancing material 1080, a material 1040 that binds to a material in the analyte sample, and a structure 1050 with or without diamagnetic, paramagnetic, or ferromagnetic magnetism applied to the surface thereof. is a perspective view.

28 is a perspective view of a process of detecting a trace amount of a target material through the diamagnetic, paramagnetic, and ferromagnetic magnetic structure and mixer of claim 5, the optical signal extraction module of claims 8 and 26, and the electromagnetic generation module of claim 13 to be.

28 (a) shows a material 1040 binding to a material in the analysis sample, a structure 1090 having diamagnetic, paramagnetic, and ferromagnetic magnetism applied to the surface thereof, and the type of nucleic acid, protein, etc., to be detected by the structure It is a perspective view of a material 1100 combined with a target material 1070 to be detected and a material 1080 including a fluorescence or Raman signal enhancing material that enhances the optical signal of the target material.

28 (b) shows an optical signal enhancing material such as a fluorescent material and a Raman signal enhancing material in the analysis sample, and a specific material such as a nucleic acid such as DNA/RNA that binds or does not bind to them, an antibody, and an antigen, and a material that binds them Nucleic acids such as DNA/RNA in which a mixture of structures having various diamagnetic, paramagnetic, and ferromagnetic magnetic properties applied to the surface is combined with an optical signal enhancing material such as a fluorescent material or a Raman signal enhancing material in the analysis sample through a material reactor or a mixer , a perspective view of the formation process of a mixture including various diamagnetic, paramagnetic, and ferromagnetic structures bound to specific substances such as antibodies and antigens.

28(c) shows various diamagnetic, paramagnetic, and ferromagnetic magnetisms combined with specific substances such as nucleic acids, antibodies, and antigens such as DNA/RNA combined with optical signal enhancing materials such as 28(b) fluorescent materials, Raman signal enhancing materials, etc. The band is a perspective view of the process in which the mixture including the structure is put into the module of FIG. 8(f).

FIG. 28( d ) is a perspective view illustrating a process of uniformly distributing the mixture in the module of FIG. 8( f ) of FIG. 28( c ) to the Ramsel substrate through the rotator 690 .

28( e ) is a perspective view illustrating a process in which a magnetic material is present near a Ramcell or an electromagnetic field is generated in the Ramcell to place the magnetic material in the Ramcell.

28( f ) is a perspective view illustrating a process of removing materials other than those located in the Ramsell through magnetism through the cleaning solution 1110 .

10: Micro-sized cell (aka Ramcell. It may contain nanoparticles therein)
20: Nanoparticles inside Ramcell
30: substrate including Ramsel
40: Ramsel's Array
50: Laser and various light source devices for SERS or TERS, SPR, IR, etc. optical signal extraction
60: laser and various rays
70: Module with optical lens and spectrometer (grid and CCD receiver).
This module may contain filters. Also, CMOS can be used instead of CCD.
An interferometer can be used instead of the optics. to contain a portion of the RPU, or to be replaced by an RPU
can It may include a beam splitter.
80: module including lens and beam splitter
90: grating, reflective grating (Dispersive Grating)
100: A photodetector such as a CCD/CMOS receiver (including electron-enhanced CCD, aka EM-CCD)
110: reflector
120: Laser or other types of light passing through or in response to light to generate photons
Ramsel
130: a substrate or material through which a laser or other types of light pass
140: module with laser diode or micro LED
150: Tip Enhanced Raman Spectroscopy (aka TERS) module
160: micro filter (including nano size)
170: micro nozzle (including nano size, including inkjet nozzle)
180: inlet temperature pressure of the filter.
190: Ramsell upper temperature pressure
200: Fluid properties and motion of a microfluidic system
210: outlet temperature pressure of the microfluidic system
220: An optical lens and a spectrometer that can be simultaneously applied to all Ram cells in the substrate including the Ram cell
module including. May include laser and TERS modules. with or with RPU
can be replaced
230: Laser or TERS that can be simultaneously applied to all Ramcells on the substrate including Ramcell
module. It may include an RPU or be replaced with an RPU.
240: a partially co-applicable optical lens and a spectrometer in a substrate including Ramsel
module including. May include laser and TERS modules. with or with RPU
can be replaced
250: partially co-applicable laser or TERS in the substrate including Ramcell
module. It may include an RPU or be replaced with an RPU.
260: motion of each module for Raman signal extraction in Ramcell
270: reflected laser
280: light source for SPR
290: module containing a light receiver from a prism or spectrometer
300: SPR prism or various spectrometers
310: a ray reflector from a prism or spectrometer
320: a module including a light receiver for a prism or a spectrometer and a light source for SPR
330: a prism or a spectrometer, and a light receiver from them and a light source for SPR
module including
340: optical lens and spectrometer (grating and CCD receiver) and laser diode or micro
Modules with LEDs. A beam splitter may be included therein,
This enables back scattering. contains RPU, or
It can be replaced by RPU.
350: TERS module with TERS signal receiving system. Include or replace RPU
can be
360: micro or nano size tip pipette
370: micro or nano controller
380: movement of flexible micro- or nano-sized tip pipettes
390: Flexible micro or nano size tip pipette
400: position marker for positioning and adjusting the position of the substrate
410: an intermediate region between the Ramsels located closest to each other
420: location line of the middle section shape of the right Ramsell
430: Ramsell target signal is extracted
440: spectrum extracted from each Ramcell
450: spectrum of reference material
460: Ramsel substrate
470: Module for processing samples for analysis distributed to Ramsell
480: Module for purifying the sample for analysis to be distributed to Ramsell
490: module for dispensing samples for analysis into Ramsell
500: Module for extracting and processing Raman signals from analytes distributed in Ramcell
510: module for extracting and processing SPR signal from analyte distributed in Ramcell
520: A new Ramcell by extracting a sample from the Ramcell determined to have a target signal
including mixing with a solution that can be put back into the Ramsel on the substrate. in Ramsell
Modules that can be distributed and re-extract Raman and SPR signals
530: Ramsel substrate through a mark that allows to measure the coordinates and height of each part
Module to measure the position of the mark by optical or physical technique
540: The Ramcell substrate determines the position of the Ramcell substrate by measuring the coordinates and height of each part.
module to change
550: A module and method for generating and modulating a magnetic or electric field in a Ramsel structure.
560: to enhance the optical signal by irradiating light on the surface opposite to the surface of the Ramcell in contact with the sample
module
570: A module and method for maintaining a constant temperature and pressure of a Ramcell substrate.
580: A cartridge containing multiple Raman substrates.
590: A module and method for generating and controlling polarity on a Ramcell or Ramcell surface.
600: The signal pattern extracted from each Ramcell is the spectrum of the reference material.
Machine learning capable of judging whether a specific pattern in the library is similar
A module that stores programs and chips that perform machine learning
610: Through the analysis result of the type and amount of the substance in the sample of Ramsel, the composition and
A module that informs the user of an attribute.
620: associated with a server in which signal patterns and pattern recognition models extracted from each Ramsel are stored
A system for sending and receiving data.
630: The user determines the type of the sample, the analysis environment conditions such as the temperature and pressure of the sample, and the
A module for entering information about the subject.
640: Determining whether the type of the sample input by the user actually matches the type of the sample
module
650: sample inlet
660: sample inlet tube
670: impeller
680: sample container holder
690: holder rotator
700: Rotating direction
710: fixed mirror
720: moving mirror
730: FT detector
740: filter
750: beam splitter
760: exhalation straw
770: sample extraction tube
780: sample container
790: solution extraction tube
800: microcontroller opener
810: ramsel edge
820: movement path of the beam
830: Transmission Grating
840: laser exit and inlet modules. It may include lenses and filters.
850: module composed of specific wavelength filter arrays
860: filter array
870: Beam Collector and Path Transformer (with Lens/Mirror)
880: substrate including RPU
890: length change module for changing the position of the board including the RPU
900: rotation module for changing the position of the substrate including the RPU
910: RPU movement direction within the RPU board
920: the direction of movement of the RPU board position change module
930: module including a reflective diffraction foot and a reflective mirror
940: Ramcell substrate containing analysis sample and module with beam splitter and lens
950: RPU data transmission/reception module
960: data storage module of RPU
970: data processing module of RPU
980: Module including emitter or photodetector of RPU
990: Module with optical lens and spectrometer (grid and CCD receiver). sample material
There is a container to hold it. This module may also include a filter. In addition
CMOS can be used instead of CCD. An interferometer can be used instead of the optics. RPU's
It may include some or be replaced by RPU. Beam Splitter
can include
1000: optical lens and spectrometer (grid and CCD receiver) and laser diode or micro
Modules with LEDs. A container capable of containing sample material is present. inside
It may include a beam splitter, through which backscattering (Back
Scattering) is possible. It may include an RPU or be replaced with an RPU.
1010: RPU
1020: SERS substrate without sample for analysis
1030: optical signal extraction module and SERS board connection axis
1040: A substance that binds to a specific substance, such as a nucleic acid, antibody, antigen, etc., such as DNA/RNA that is not bound to or is not bound to a fluorescent substance, a Raman signal enhancing substance, etc. in the analysis sample
1050: A structure with various diamagnetic, paramagnetic, and ferromagnetic magnetism or no magnetism applied to the surface of a substance binding to a specific substance in the analysis sample
1060: Parts or regions containing diamagnetic, paramagnetic, ferromagnetic materials or generating magnetic fields
1070: Substance containing the type of nucleic acid, protein, etc. to be detected
1080: A material containing a type of fluorescence or Raman signal enhancing material that enhances the optical signal of the target material to be detected
1090: Various diamagnetic materials coated on the surface of a substance that binds to a specific substance, such as nucleic acids, antibodies, antigens, such as DNA/RNA, which binds or does not bind with an optical signal enhancer such as a fluorescent substance or a Raman signal enhancer in the analysis sample, Paramagnetic and ferromagnetic structures
1100: A structure having various diamagnetic, paramagnetic, and ferromagnetic magnetisms combined with specific substances such as nucleic acids, antibodies, antigens, such as DNA/RNA, combined with optical signal enhancing substances such as fluorescent substances and Raman signal enhancing substances in the analysis sample
1110: Various diamagnetic, paramagnetic, and ferromagnetic magnetic structures bound to specific substances such as nucleic acids, antibodies, and antigens, such as DNA/RNA, combined with optical signal enhancing substances such as fluorescent substances and Raman signal enhancing substances in the analysis sample, electromagnetic fields A cleaning solution that removes materials that are not bound to structures with diamagnetic, paramagnetic, or ferromagnetic magnetism without interfering with the generation of
1120: Substance other than the substance to be detected in the sample

Claims (29)

Board;
A substrate containing several cells of the same design and size with a minimum size (~ laser wavelength) that can extract Raman signals and various optical signals. Here, each cell refers to an area in which an analysis sample, which is an object of optical signal extraction of each optical signal extraction module of claim 8, is located. As in claim 3, when the cell may not have a specific structure and has a planar shape, the Ramcell substrate is a planar substrate. The present invention efficiently extracts the optical signal of a trace material contained in each volume in consideration of the effect that the type and amount of the material contained in each volume decreases as the volume of a given sample is divided, and extracted from these unit volumes. Based on all optical signals, it is possible to determine the type and amount of the overall substance in a given sample.
The above-mentioned cell is referred to by the inventor as Ramcell.
A substrate including the above-mentioned Ramcell is referred to as a Ramcell substrate.
When the lens of the optical signal extraction module and the analyte come into contact with each other, the lens surface of the optical signal extraction module may serve as a Ramcell.
The Raman signal mentioned above refers to the Raman spectrum or Raman imaging.
The Ramsel substrate may include a mark that allows the coordinates and height of each part to be measured.
Nanoparticles capable of enhancing the Raman signal size may be included inside the Ramcell.
Ramcell itself may be a variety of diamagnetic, paramagnetic, and ferromagnetic materials that can attract metals and semiconductor materials with attraction, and may contain various diamagnetic, paramagnetic and ferromagnetic materials or be associated with components that generate magnetic fields.
Ramcell is the minimum size from which the Raman signal is extracted and includes a sample for analysis to be analyzed.
The number of Ramcells on the substrate may be determined according to the type and characteristics of the sample to be analyzed (concentration, viscosity, surface tension, etc.).
The size of Ramcell can also be determined according to the type and characteristics of the material to be analyzed (size of internal cells or polymers to be detected, viscosity or surface tension of the sample, etc.).
The number and size of the Ramcell may be designed according to the sample to be analyzed and the purpose.
The size of the Ramcell should be designed to minimize the increase in the temperature of the material in the Ramcell by the laser and to extract the spectrum of all materials as much as possible in the sample in the Ramcell. In particular, the biosample is damaged as the temperature rises, and the Raman signal may vary. Therefore, the initial temperature rise of the material by the laser can be predicted by considering the laser intensity (eg, mW/μm2), the beam size, the laser incident duration, and the specific heat of the material that meets the Ramsel material surface. Depending on the thermal conductivity, specific heat, and contact surface of the Ramcell substrate and the gas in contact with the material in the Ramcell, the time required to reach the equilibrium state and the temperature at the equilibrium state can be predicted. After measuring the range from the maximum temperature rise of the substance in Ramsel to the equilibrium temperature, the temperature-dependent spectrum within this range matches the spectrum expected at the initial temperature at the time of measurement of the sample in the library according to claim 19 . and can be designed to be above a certain level. Of course, if there is a heat exchanger around the Ramsell substrate, it should be designed in consideration of heat exchange efficiency. The size of the Ramsel must be at least larger than the largest particle in the sample to be distributed in the Ramsel. For example, when analyzing the internal composition of blood, the size of the Ramcell can be largely determined based on the size of blood cells, plasma, pathogens, and the like. Blood cells such as red blood cells and platelets, including leukocytes such as granulocytes, macrophages, lymphocytes, and dendritic cells, and bacteria are usually in the micrometer unit, while plasma such as globulin and albumin, cancer biomarkers, and viruses are in the nm unit. Therefore, the minimum size of the Ramcell may be different when only the plasma portion of the blood is distributed to the Ramcell by filtering and when all the composition of the blood is distributed to the Ramcell without filtering.
When the total amount of sample to be analyzed is determined and the optical signal is extracted by distributing them to the Ramcell for analysis, as the number of Ramcells increases, the Raman signal of a trace amount of the target material to be measured becomes more pronounced compared to other materials, making it more clear more likely to be extracted. For example, if the number of trace substances A in one Ramcell is one and the number of large substances B is ten thousand, if one Ramsel is increased to two Ramsels and the amount of substances is distributed as much as possible, then there are 5,000 substances B in one Ramsel. , and there is no substance A, but in the other Ramcell, there are five thousand substances B and one substance A. Therefore, the optical signal of material A is relatively large compared to the optical signal of material B. As a similar example, if the number of Ramcells is increased to ten thousand and distributed in the same amount as possible, one substance B and one substance A exist equally in any one Ramcell. The minimum number of Ramcells that makes the optical signal of material A stand out from the optical signal of material B may vary depending on the optical signal pattern, laser wavelength and power, Ramcell size, material and pattern of each material. Therefore, after estimating an appropriate minimum number of Ramsells through electromagnetic field simulation, an appropriate number may be determined through an actual experiment, or an appropriate number may be determined through an experiment alone. Likewise, in order to separate trace substances from many types of large substances, the minimum number of Ramsells that allow the trace substances to appear conspicuously is measured through simulations and experiments.
When the amount of sample to be injected into Ramcell is determined, the number of molecules entering the Ramcell of a given size can be reduced by diluting the analyte sample to lower the concentration, but the total number of Ramcells must increase by the dilution factor of the substance. Assuming that the volume of substance molecules injected into a Ramcell can be neglected, the average number of specific substances in an analyte sample entering a Ramcell is the total amount of specific substances in the total analyte sample mobilized for analysis divided by the total number of Ramcells , the number of specific substances per one Ramsell may depend on the Poisson distribution. Different optical signals from each Ramcell are helpful for characterization, such as the type and concentration of substances.
It is possible to library optical signals for substances in each Ramcell. The optical signal may be changed according to the type and properties of the material (concentration, viscosity, etc.). For each pure substance and mixture, it can be modeled through machine learning through optical signal data extracted from each experimental condition. To obtain sufficient data to obtain a valid model, we can determine the total number of Ramsels required for the analysis.
When the total number and size are determined in consideration of the above conditions of the total number of Ramcells and the size of Ramcells, the size of the Ramcell substrate and the number of Ramcells per Ramcell substrate are determined, and then the total number of required Ramcell substrates is also determined.
The material and surface composition and surface treatment of Ramsel according to claim 1 .
Materials and surfaces of Ramcell are materials or surfaces that can efficiently amplify the Raman signal or help the analysis sample move into the Ramcell. In general, plasmonic materials such as Au and Ag are used for SERS, as well as noble metals such as SiO2 and Si3N4, which are insulators, and other materials such as Si and GaAs with semiconductor properties. Materials with semiconductor properties not only induce electric field enhancement like noble metals, but also induce magnetic field enhancement and can be used to inhibit temperature rise due to hot spots. For example, it is known that the temperature rise caused by Si nanoparticles is lower than that caused by hot spots generated by Au nanoparticles of the same size, shape, and arrangement. This may be easy to analyze samples containing temperature-sensitive cells or polymers. In addition, when oxygen is added to the semiconductor material, since there is a surface enhancement effect, the semiconductor material and surface to which oxygen or various other chemical substances are added also fall within the scope of the claims.
Ramsel may be a variety of diamagnetic, paramagnetic, and ferromagnetic materials.
The types of materials of Ramcell include various diamagnetic, paramagnetic, and ferromagnetic materials. When a component that generates a magnetic field allows nano- or micron-sized particles of metallic or semiconductor properties to be positioned in the Ramsel through attraction, it contains a material that minimizes the reduction in attraction.
The Ramcell may be simply made of nanoparticles or a substrate material made of a material having a metal or semiconductor property. It is not limited to the material of the metal and may be composed of various organic and inorganic chemicals including graphene. By adding elements such as nitrogen or boron to graphene, free electrons or holes can be increased, which can help amplify optical signals. In addition, adding conductive nanoparticles such as copper or gold to graphene can help amplify optical signals. Various chemical additions to graphene can be realized through CVD techniques.
In consideration of surface tension or viscosity, a material having hydrophobicity and hydrophilicity may be applied to the surface of Ramcell, or Ramcell itself may be composed of a material having hydrophobicity and hydrophilicity. Depending on the purpose, the Ramcell surface may be treated with an antibody, antigen, aptomer, or other various chemicals that bind to substances in the sample located in the Ramcell region.
Ramsell's materials and surface composition and treatment methods vary widely. Various substitutions, modifications and changes will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention.
The design of claim 1 , wherein the Ramcell and the nanoparticles within the Ramcell are.
Ramcell and the design of nanoparticles in Ramcell may vary depending on the characteristics of the sample for analysis distributed in Ramcell. For example, when the sample for analysis is a fluid material, the Ramcell may be engraved to form a microwell, and nanoparticles inside the microwell may be embossed or engraved. The mentioned microwells are not limited to the micron size and may be of various sizes, but are a word used to refer to the engraved Ramcell. The mentioned nanoparticles are also not limited to nano size and may have various sizes, but are smaller than Ramsel. In addition, when the sample for analysis is a material with low fluidity, the Ramcell is configured in a flat or embossed shape, and nanoparticles in the Ramcell region may be formed in a negative or embossed shape. Ramcell and the design of nanoparticles within Ramcell are possible in shapes other than embossed and engraved. If the Ramsel itself is in the form of a container for containing substances, it may have various shapes, such as cubic, bowl, and triangular pyramid. According to the size and shape of nano- or micron-sized particles with diamagnetic, paramagnetic, and ferromagnetic properties, the Ramcell must be designed so that these particles can be placed in the Ramcell. The Ramcell should be designed so that the laser can target the particles well to each material in the Ramcell, and the scattered light should be positioned and designed so that the scattered light enters the lens of the optical signal extraction module as much as possible. Nanoparticles should be designed to amplify optical signals. The amplification effect can be verified through experiments, but the initial design and design direction can be established through electromagnetic field simulation (eg, finite-difference time-domain, so-called FDTD) or existing data or theory. The characteristic length representing the size and shape of each Ramcell and the nanoparticles in Ramcell is set, and the size of their constituent elements is stored in the library of claim 19 and updated to determine the amplification effect of optical signals and each element correlations with their size can be found. When an analyte is dispensed into a Ramcell, if it is a solution, the Ramcell must be engraved to contain the analyte. Therefore, if the lens of the optical signal extraction module contains the analyte, the shape of the lens is preferably concave. A general conductor or semiconductor substrate without an optical signal extraction module can be designed with a concave Ramcell through etching or thin film. In addition, the shape of a triangular pyramid, square pillar, cylinder, and crossed nanowires are better for the amplification effect of nanoparticles than round ones. Even if the nanoparticle size is too small, it is not good for the amplification effect, and the largest size of the amplification effect can be determined for each type of nanoparticles in the characteristic length of 60 nm to 100 nm. The distance between the nanoparticles and the analyte should be designed to be 3 nm or less to have good amplification effect, but the gap can be very diverse in the range where a sufficient optical signal is emitted. Therefore, in order for the analytes to be sufficiently close to the nanoparticles as much as possible, the nanoparticle form of Ramcell should be designed, and the amount and distribution method of the analyte per Ramcell should be determined. Ramsell can be designed to play multiple times. Therefore, the type, amount, flow rate, and Ramcell design of the regeneration solution or gas must be determined so that the Ramcell is not deformed by the regeneration solution or gas. Therefore, crossed nanowires or pillars or cones with a small aspect ratio are more suitable as nanoparticles for the reproduction substrate than a pillar shape with a large aspect ratio.
Ramcell and the design of nanoparticles within Ramcell vary widely. Various substitutions, modifications and changes will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention.
[Claim 4] The method of claim 3, wherein standardized Ramsel and internal nanoparticles are prepared.
Normalized Ramcell and internal nanoparticles can be constructed by exposure, etching, and deposition. In order to mass-produce a substrate including Ramcell, it can be designed by applying various exposure, etching, and deposition methods used in the semiconductor process. The pattern is exposed and developed on the substrate coated with photoresist through a mask and exposure equipment optimized through Optical Proximity Correction (OPC) in consideration of Ramsell’s design. It is possible to engrave embossed and engraved Ramcell and nanopatterns by depositing a material for engraving and repeating exposure and etching. In order to realize sophisticated Ramcell and nanopatterns, exposure equipment using light sources such as DUV and EUV, deposition equipment for atomic layer deposition, and high aspect ratio etching equipment can be used. Of course, depending on the purpose, exposure equipment, deposition equipment, and etching equipment having higher or lower specifications may be used. And, it includes all materials and parts necessary for the use of each equipment. The standardized Ramcell manufacturing method is not limited to the semiconductor process. In addition to the semiconductor process, various manufacturing methods that can achieve standardization of Ramcell are also included. For example, 3D printers can also achieve standardization of Ramsell. The use of 3D printers to create models based on metal and polymer materials and other molding technologies are also included in the bill. Here, the standardized Ramcell refers to a Ramcell that can be repeatedly manufactured and reproduced in terms of the design and size of the Ramcell. After stacking nanowires and other nanoparticles of various shapes, they can be thinned with metal, semiconductor, or insulator to form nanoparticles in Ramcell.
The module, material and method of claim 1 , for obtaining or processing a sample for analysis that is dispensed into a Ramsel.
In order to correctly locate the material in the sample for analysis or to effectively extract the optical signal, the characteristics of the sample for analysis at the time of initial acquisition may be changed. For example, if the surface tension of the sample is large, it may be difficult to insert the sample into the ramcell in the form of a microphone well, and thus the surface tension may be weakened by various chemical and physical techniques. Various surfactants may be chemicals that can weaken the surface tension. In addition, the viscosity and adhesion of the sample for analysis can be changed with various chemical and physical techniques so that the analyte can be evenly distributed and settled in Ramcell. Various types of chemical methods including physical methods including vibration and rotation to evenly mix the samples for analysis and methods of mixing with chemicals that help the hydrophobic and hydrophilic functional groups of the materials in each sample for analysis can be used. have. In order to give polarity to the material in the sample, it can be processed into an anion or a cation by reacting the material. By combining the material in the sample with a diamagnetic, paramagnetic, or ferromagnetic material, an attractive force can be applied to the Ramcell surface with a magnetic field, and the strength of the surface plasmon can be strengthened. The substance can be made into a gel form or injected into the gel. By extracting a sample from Ramcell again, it can be evenly mixed with a solution that can be redistributed to Ramcell on a Ramcell substrate and then distributed to Ramcell again. To reduce the concentration of the sample, the sample solution can be diluted in distilled water or a substance such as acetone that evaporates quickly. For example, a drop of blood can be diluted in distilled water. Dilution can lower the concentration of a substance, reducing the number of molecules in the Ramsel. In addition, diluting the colored material reduces the intensity of Rayleigh light, which can help in efficient optical signal extraction. The total number of Ramcells and the size of each Ramcell should be determined, taking into account the sample volume increased by the dilution factor and the decreased concentration. To concentrate biomarker samples related to respiratory diseases, a person suspected of being a patient coughs or exhales through a straw or various tubes in a container containing distilled water or other substances that dissolve the biomarker sample to obtain the biomarker. can By coughing and exhaling several times, the concentration of the biomarker in the dissolved substance can be increased. In the case of blood, it can be obtained with a micro-syringe that minimizes the suffering of humans or other animals.
This section includes materials that combine with an analyte sample material to aid in efficient optical signal extraction. It is possible to use structures of various bell shapes and materials, including small spheres in which a substance binding to a specific substance is applied to the surface of the substance in the sample dispensed to the Ramsel. Analytes and small structures capable of collecting them and amplifying the optical signal may be mixed prior to distribution to the Ramcell, or may be distributed to the Ramcell simultaneously or in a different order. In combination with other specific substances, it includes substances that amplify optical signals electromagnetically or chemically.
A target material can be collected in such a structure through a material that binds to a material in the analyte sample and a structure with or without diamagnetic, paramagnetic, or ferromagnetic magnetism applied to the surface thereof. The shape can vary greatly depending on the bonding material and structure. A target material to be detected, a material containing a fluorescent or Raman signal enhancing material that enhances the optical signal of the target material, a material binding to the material in the analysis sample, and a diamagnetic, paramagnetic, or ferromagnetic magnetic structure coated on the surface Through the coupling between the electromagnetic field of the Ramcell and the magnetic material, the magnetic structure combined with the target material can be collected into the Ramcell.
Efficient mixing of substances can be achieved in a small mixer with an impeller or by shaking or repeatedly inverting the container. The temperature of the mixer can be adjusted. When the nucleic acids in the original sample are bound to each other, the temperature may need to be adjusted so that they can bind to different types of nucleic acids. It is also possible by several mixers like other static mixers. Metal nanoparticles or fluorescent materials can be bound to the sample for optical belief amplification. If the initial sample material is a gas or a solid, it can be analyzed by dissolving them in a solution.
Modules and methods for obtaining or processing analytes in Ramcell on a substrate are very diverse. Various substitutions, modifications and changes will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention.
The module and method according to claim 1, for purifying the sample for analysis to be distributed to Ramsel.
It is possible to purify by differences according to physical and chemical properties such as density, viscosity, size, boiling point, melting point, freezing point, hydrophilicity, hydrophobicity, and magnetism between substances in the sample of the previous type of analyte distributed in Ramsel. The module for purifying the sample may include a centrifuge enabling purification by a difference in density and a filter system enabling purification by a difference in size. A filter system can be made by composing nano-size or micro-sized beads, and can be made by stacking nanowires. A filter system can be formed through artificial and natural high-polymer materials with small passageways and substrates with nano- and micro-sized pores.
The module for distributing to Ramsell may include a filter system. Figure 8 reflects an example of this.
When the analyte distributed in Ramsell is absorbed by cotton or various fibrous or polymeric chemicals, the material can be extracted by physically compressing them.
Modules and methods for purifying a substrate for analysis are very diverse. Various substitutions, modifications and changes will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention.
The method according to claim 1, wherein the sample for analysis, the colloid of nanoparticles for optical signal enhancement, a fluorescent material or a Raman signal enhancement material, a magnetic material, or a material capable of binding to a specific sample material is distributed to the Ramcell, or the material of the target Ramcell after dispensing Modules and methods for reacquiring and redistributing
The method of dispensing to Ramsell is nano- and micro-size fluidic (microfluidic) format, and inkjet nozzle format. These include nano- and micro-size pipettes, gel cutting, compression, and attraction through electromagnetic fields and materials with magnetism. Figure 8 reflects an example of this. In order to extract an efficient optical signal, it may be necessary to enhance the adsorption of the material to the surface of Ramsel. Therefore, the Ramsel solution can be evaporated after dispensing. It should be ensured that the light substances in the Ramsell are not lost by natural evaporation, gas flow, or forced evaporation due to changes in temperature or pressure.
As the sample moves through the nano- and micro-fluidic system, an electromagnetic field may be generated depending on the characteristics of the target material in the sample, or it may be located in a Ramcell coated with a material such as an antibody, antigen, and aptomer that binds to the sample.
This section includes nano- and micro-sized pipettes for re-acquisition and redistribution of Ramcell material from which the target material has been found. In addition, metal nanoparticles colloids or fluorescent materials can be distributed for signal amplification through the module of this section.
There are many different modules and methods for dispensing the analyte of the substrate. Those of ordinary skill in the art within the scope that does not depart from the spirit of the present invention described in the claims
Various types of substitution, modification, and change will be possible by those skilled in the art, and this also falls within the scope of the present invention.
The module and method according to claim 1, for extracting and processing a Raman signal from the analyte distributed in Ramcell.
Modules that can extract Raman signals from two or more Ramcells at once can be arranged to quickly extract Raman signals from multiple Ramcells. This module may include the RPU mentioned in claim 20 . As mentioned in claim 1, an optical signal is extracted by dividing the volume of a given sample by a unit volume, and it is a module for efficiently and quickly extracting an optical signal of a large unit volume. Modules that can extract these Raman signals include gratings, beam splitters, filters, lenses, and spectroscopic systems including CCD and CMOS, Fourier Transform (aka, FT) systems, lasers, LEDs or TERS such as reflection and transmission diffraction fields. include In addition, it includes modules necessary for spectroscopic techniques such as Transmission Raman Spectroscopy (aka TRS) and Spatially Offset Raman spectroscopy (aka, SORS). There is no limitation on the range or type of the wavelength of the laser. It includes both lasers using gases such as Argon, Krypton, and CO2, and diode lasers using semiconductors such as neodymium-doped yttrium aluminum garnet (NeYAG). A laser module may contain one or several diode lasers comprising various semiconductor materials generating each desired wavelength. Infrared and visible laser diodes can be made by utilizing semiconductors such as InGaN, AlGaInP, GaAlAs, InGaAsP, and GaInAsSb. It includes a photodiode that can convert light energy of various wavelengths into electrical energy by using materials other than the indium-gallium-arsenide (InGaAs) detector used in the FT Raman analyzer.
In order to use several types of laser wavelengths, the laser corresponding to each wavelength and the filter suitable for the pass can be automatically replaced. The power can be adjusted for each laser wavelength. Long-wavelength lasers such as 1064 nm or 1280 nm are required to reduce fluorescence as much as possible. In order to intensify the stokes spectral intensity, the power can be increased within a range that does not destroy the biosample or the sample temperature can be increased. Modules in this section include tunable or pulse type lasers. There is no limit to the number of modules of the laser. Laser filters include notch filters or edge filters. There are various methods for making such a device as shown in FIGS. 4 to 7 .
Depending on the rotation direction of light, the optical signal may be different depending on the chirality of the material in the Ramcell. Therefore, this Raman signal extraction module may also include a module for inducing rotation of light.
Ultimately, so that optical signals can be simultaneously extracted from all Ramcells, the system must be capable of processing all optical signals emitted by samples in Ramcells by allowing lasers to enter all Ramcell regions at the same time. When the size of the Ramcell or the size of the optical module does not allow this, a module that extracts and processes Raman signals of one or more Ramcells or a Ramcell substrate can extract and process Raman signals while the substrate moves. The movement method includes various types of Scanner or Stepper methods. Such an optical signal extraction module may extract an image or spectrum while one unit or one or more units are fixedly located in a specific area, or moved step by step or continuously moved by a movement module. The laser module, the laser reflector module, and the module including the optical lens and the spectrometer are separated, and the laser path is changed through the laser reflector to make the laser move to the module including the specific optical lens and the spectrometer. And the server or the device of claim 18 may include a module that can transmit and receive wired or wireless.
This claim includes a module including a laser diode or micro LED under which a substrate or material through which a laser or other types of light passes is located under the Ramcell. Above the Ramsel is placed the module containing the optical lens and the spectrometer (the grating and the CCD receiver). Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.
This claim includes modules containing laser diodes or micro LEDs under the Ramsel. Above the Ramsel is placed the module containing the optical lens and the spectrometer (the grating and the CCD receiver). This module may contain a part of the RPU, or may be replaced by an RPU. A module containing a laser diode or micro LED is located under the Ramsel. Modules including optical lenses and spectrometers (lattice and CCD receiver), lasers for SERS, and various light sources are located on Ramsell. Ramsell and lenses can come into contact. There may be a material through which light passes between the laser and the substrate.
This claim includes modules including TERS, optical lenses and spectrometers. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.
This claim includes a module in which a TERS module including a TERS signal receiving system is located above the Ramcell. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.
This claim includes modules in which optical lenses and spectrometers (lattice and CCD receivers) and modules including laser diodes or micro LEDs are located on the Ramsel, as well as the TERS module without the TERS signal receiving system. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.
This claim includes a module comprising an optical lens and a spectrometer (a grating and a CCD receiver) on a Ramsel. Tip Enhanced Raman Spectroscopy (TERS) modules are located there. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU. A module containing a laser diode or micro LED is located under the Ramsel.
This claim includes a Ramcell including a TERS module and a module including an optical lens and a spectrometer. Above the Ramsel are placed optical lenses and spectrometers (grids and CCD receivers) and modules containing laser diodes or micro LEDs. Ramsell and lenses can come into contact. This module may contain a part of the RPU, or may be replaced by an RPU.
There may be a space for storing an analyte in the photodetector, and there may be an optical signal amplifying substrate on the top. Therefore, in this case, the photodetector acts as a Ramsel. There is a lens through which the laser passes on the top of the substrate, and there is a light emitter on top of the lens.
An optical signal extraction module composed of a single diffraction foot that simultaneously extracts optical signals from each Ramcell or extracts them by time can be configured. The light emitter located at the top of each Ramcell shoots a laser on the Ramcell analysis sample, and the scattered light passes through the beam splitter and lens module, enters the module including the reflective diffraction foot and the reflective mirror, and reflects the scattered light from each Ramcell. and a method in which light is diffusely diffracted by a single reflective diffraction foot through a reflective mirror and enters a photodetector configured in parallel by a reflective mirror configured in parallel. In addition, the light emitter located at the top of each Ramcell shoots a laser at a specific time to the analysis sample of the Ramcell, and the scattered light passes through the beam splitter and lens module, collects the beam and uses the path converter (including the lens/mirror) to reflect the diffraction foot and the reflection mirror. It is sent to the containment module, is diffusely diffracted by one reflective grating through the reflective mirror, and then enters the photodetector by the reflective mirror again.
The position of the laser beam on the sample surface in the Ramcell can be fixed or can be moved. Once fixed, it is necessary to adjust the laser power, duration, and the time it takes to re-radiate the laser in consideration of the change due to heat in the sample in the Ramcell. The duration shall be constrained to be lower than the maximum temperature allowed for the sample in the Ramcell as mentioned in paragraph 1 and shall be ranged to be greater than the time it takes for as much as possible all material in the sample in the Ramcell to enter the range of the beam by diffusion. can The maximum diffusion time for the material in the Ramcell to enter the beam range can be estimated as the square of the distance from the edge of the Ramcell to the beam position divided by the diffusion coefficient. Since the movement of the laser beam in an ascending Ramcell avoids a local temperature rise and can induce scattering of light for as many compositions as possible of the sample in the Ramcell, it is also within the scope of the claims that the movement of the beam is designed to be necessary. . The movement of the beam is possible by movement of the inner lens or reflective glass of the laser module or movement of the module itself. Movement ranges and movement patterns can vary widely. The movement of the beam can be repeatedly rotated around the frame in the Ramsel, starting from the center of the Ramsel and moving to the frame in a whirlpool, or vice versa, starting from the frame and moving to the center of the Ramsel, and moving in a zigzag from one side of the Ramsel to the other. The starting point and the ending point can be very different. It is possible to move to an arbitrary pattern in Ramsell rather than a fixed pattern.
The Raman signal extraction module may simultaneously extract optical signals for one or more samples of Ramcell.
The module for extracting and processing the Raman signal may be combined with the distribution module of claim 7 or included in the distribution module.
It is not limited by the above-described embodiments including and the accompanying drawings, but may be defined by the appended claims. Accordingly, various types of substitution, modification and change will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention .
The module and method according to claim 1, for extracting and processing the SPR signal from the analyte dispensed in Ramsel.
Modules capable of extracting SPR signals from two or more Ramcells at once can be arranged to quickly extract SPR signals from multiple Ramcells. It includes a module that can extract SPR signals. Methods for making such a device are various as shown in FIGS. 10 to 11 . At the same time, a module that extracts and processes SPR signals from multiple Ramcells or a Ramcell substrate can extract and process SPR signals while moving. It is not limited by the above-described embodiments including and the accompanying drawings, but may be defined by the appended claims. Accordingly, various types of substitution, modification and change will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention .
10. The method of claim 8 and 9, comprising the process of extracting a sample from a Ramcell determined to have a target signal and mixing it with a solution that can be put back into the Ramcell on a new Ramcell substrate. Modules and methods that can be distributed to Ramsel and re-extract Raman and SPR signals.
This process may be repeated so that the user is satisfied with signal extraction of the desired target material. PCR and ELISA can be performed in the Ramcell determined to have the target signal, or the sample in the Ramcell can be moved to the PCR and ELISA module for analysis. It is not limited by the above-described embodiments including and the accompanying drawings, but may be defined by the appended claims. Accordingly, various types of substitution, modification and change will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention .
The module according to claim 1, wherein the Ramsel substrate measures the position of the mark by an optical or physical technique through a mark that allows to measure the coordinates and height of each part.
The module according to claim 11, wherein the Ramcell substrate changes the position of the Ramcell substrate by measuring the coordinates and height of each part.
The position of the Ramcell can be changed so that the laser beam is correctly positioned on the sample surface in the Ramcell.
The module and method of claim 1 , wherein a magnetic or electric field generation and regulation module and method in a Ramcell structure.
A Raman signal or various plasmon signals can be enhanced through a magnetic field or a magnetic field. The magnetic field can be generated and the strength can be adjusted through electric current so that diamagnetic, paramagnetic, and ferromagnetic nanoparticles or micron-sized particles, etc., are placed in the Ramcell by attraction.
A module capable of generating a magnetic field through a coil wound around a nano- or micron-sized wire may be included in, in contact with, or exist in the vicinity of the Ramcell. The strength of the magnetic field can be strengthened by flowing a strong current or increasing the number of coils. In addition to magnetic fields, electric fields can also help to amplify the signal. By amplifying an optical signal having a weak intensity of a specific frequency through an electromagnetic field of the same frequency, the existence and intensity of the optical signal can be measured. Modules with various diamagnetic, paramagnetic and ferromagnetic materials can be used. Various substitutions, modifications and changes will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention.
The module and method according to claim 1, wherein the optical signal is enhanced by irradiating an electromagnetic field and light of a specific frequency to the surface opposite to the surface of the Ramcell in contact with the sample.
In order to enhance the surface plasmon of the Ramcell, a photon may be shot on the surface opposite to the surface of the Ramcell in contact with the sample, or the photon may be penetrated. In general, the wavelength of plasmon of metal is close to visible light and ultraviolet light. It is possible to enhance plasmon resonance by shooting solid-state AlGaN UV LEDs, UV lasers formed by using filters such as quartz or fluorite in smartphone flashes, or UV lasers made using other gases at the plasmon surface. In addition, infrared and visible light can be generated through a laser diode using semiconductors such as InGaN, AlGaInP, GaAlAs, InGaAsP, and GaInAsSb, and these can be used to enhance optical signals.
When the intensity of the wavelength of a specific frequency of the Raman spectrum is weak, it may be difficult to detect. Therefore, in order to determine whether a photon having a specific frequency is generated and the intensity thereof, an electromagnetic field of the same frequency may be applied and amplified by resonance. There are many different ways to apply an electromagnetic field. Electromagnetic fields can be induced through solenoids, magnetic or diamagnetic objects, and FN tunneling of semiconductors (aka, Fowler Nordheim Tunneling). By controlling the frequency and strength of the electromagnetic field, it induces amplification of a specific optical signal.
The module and method according to claim 1, wherein the temperature and pressure of the Ramsel substrate are constantly maintained and changed.
Matter is affected by temperature and pressure. A module for maintaining the temperature and pressure of the Ramcell substrate in order to extract an optical signal for a material of a user's desired shape may be in, in contact with, or positioned above or below the Ramcell substrate. As the temperature rises, the signal of anti-stokes may become stronger. Therefore, multiple spectral extractions according to changes in temperature can be a clue to identify substances in a sample. MEMS heat exchangers including microcoolers and heaters may be located on or near each surface of the Ramsel substrate on which the sample is placed. Since materials are often measured at room temperature of atmospheric pressure, the conditions of atmospheric pressure and room temperature should be maintained in the device.
The cartridge according to claim 1, comprising one or more Raman substrates.
By storing multiple Raman substrates in the cartridge, multiple Raman substrates can be used continuously in real time for general material analysis of a specific sample, and multiple Raman substrates can be stored for subsequent analysis. The Raman substrates of the cartridge may be input to the analysis equipment until the analyte to be found is released, and when the analyte to be found is released, the input of the Raman substrate into the analysis equipment may be stopped. This section includes a cartridge for storing the analyzed Raman substrate and a cartridge for cleaning them. It can be dried after washing. It can be recycled and used again after washing. The type, flow rate, and amount of the solution or gas used for cleaning for regeneration may vary depending on the design and size of the Ramcell substrate for regeneration, but should be determined within a range that does not change the design of the Ramcell substrate. In general, as the Reynold number, which is proportional to the flow rate and the inner diameter of the tube and inversely proportional to the dynamic viscosity of the fluid, increases, the turbulence approaches and may cause deformation of the Ramsel substrate. However, since turbulence can be helpful for efficient cleaning of materials in Ramcell, it is helpful in design to find the maximum Reynold number that minimizes deformation in the design of Ramcell substrates.
The module and method for generating and controlling polarity on a Ramcell or Ramcell surface according to claim 1 .
The accuracy and sensitivity of analysis can be improved by drawing polar substances such as cations and anions in the sample for analysis into the polar Ramcell. A module that causes an increase or decrease of electrons in Ramcell is required. Using a semiconductor, this can be achieved by the movement of electrons through voltage, such as the FN tunneling technique. Alternatively, a material rich in electrons or protons can be applied to the Ramsel surface. In addition, since plasmon enhancement is possible by the free electrons of the Ramcell, the amount of free electrons can be increased through the artificial polarity generation of the Ramcell.
18. The assay platform device or component according to any one of claims 1 to 17 made using, in part or integrally, the technology of each of the claims.
Using the components of the instrument, it is possible to analyze the type and amount of substances in the sample for analysis of Ramsel. It is a platform for material analysis that separates the optical signal of a substance present in a trace amount in the sample for analysis from the optical signal of a large amount of material, and accurately measures the type and amount of all substances in the sample. For each material, the type and amount of the material in the sample can be measured through the optical signal big data obtained under experimental conditions such as temperature and concentration and the model they represent.
An optical signal extraction module, a module including a Ramsel substrate or a material-free SERS substrate, and a material distribution module are all combined and can be carried as a single device. A module including an optical signal extraction module, a Ramcell substrate or a SERS substrate can be connected by a connecting shaft, and can be unfolded during material analysis. For the material analysis module, place the sample into the sample inlet of the material dispensing module. When the optical signal extraction module includes a container containing a substance, the substance dispensing module is attached to the optical signal extraction module to dispense the substance. And after attaching the module including the SERS substrate on the optical signal extraction module, material analysis is performed. When the optical signal extraction module does not have a container for containing the material, the material is dispensed by attaching the material dispensing module to the module including the Ramsel substrate. Then, after attaching the optical signal extraction module on the module including the Ramcell substrate, material analysis is performed.
19. The method of claim 18, wherein in order to determine the type and amount of the material of the sample for analysis of each Ramcell, the optical signal data and model library software for the reference material to be analyzed and compared with the signal pattern extracted from each Ramcell; storage device.
The method according to claim 18, wherein software in the form of a library of material spectra serving as a reference for comparative analysis with the signal pattern extracted from each Ramcell may be installed. One or more modules in which this library is stored may exist in the analysis platform device of claim 18 or the server of claim 22, and may exist in parallel in the form of micro-sized or larger on each Ramcell surface. The spectrum is affected by the orientation of the material on the plasmonic surface of the material in the Ramcell, the type and angle of incidence, temperature, pressure, and the concentration of the material. It is possible to secure and library big data for reference. Big data optical signals for each material can be extracted from Ramsell. The content of big data includes material properties (chemical composition and composition), information on Ramcell substrates (eg size, number of Ramcells, etc.), analysis conditions (eg mass of material, temperature, pressure, laser wavelength, etc.) ), information about the subject of the substance (e.g., physical, social, economic, environmental information such as physical condition, race, age, pre-existing medical history, occupation, income, location of residence), Ramsell design (e.g., Ramsel's Store the optical signal data extracted from each Ramcell for size, shape, material and nanoparticle size, shape, arrangement, etc.) , through which it is possible to model the optical signal pattern for each material.
The method of claim 18, wherein machine learning capable of determining whether a signal pattern extracted from each Ramcell is similar to a specific pattern in a library of optical signals of a reference material, and forming a pattern model based on signal pattern big data is possible A program and a chip module that can do it. If the same machine learning program or library exists in the server of claim 22, it includes software that can access it.
The spectrum of a reference substance is a library of spectra of each substance that has already been discovered or a spectrum of each newly discovered substance. can For matching, Principal Component Analysis (aka PCA), Partial Least Squares (PLS), Convolutional Neural Network (aka CNN), Support Vector Machine (aka SVM), etc. Various machine learning techniques can be utilized. One module in which this program is stored may exist, and such a module may exist in a size of micro or larger on each Ramcell surface. A module including an analysis processing unit that enables parallel computing or that can perform parallel computing or a processing unit that transmits and receives optical signals for parallel computing is called a RamCell Processing Unit or RamCell Processing Unit (aka, RPU) do. In addition, a library module having a micro size or larger on the Ramcell surface of claim 19 may be present in the RPU. The RPU may include the optical signal processing device of claim 8 . Through the RPU and the overall composition library of a specific sample type, it can be determined whether it matches the sample type input by the user. Through each RPU, the type, amount, and characteristics of each Ramsel substance can be identified. Therefore, if the RPU includes an optical signal extraction module that enables parallel computing, and hardware and software for data storage, processing, and transmission/reception, the type, amount, and characteristics of each Ramcell material can be identified through each RPU.
19. The method of claim 18, wherein the composition and characteristics of the sample are informed to the user through the analysis result of the type and amount of the substance in the Ramsel sample, and the user determines and informs whether the type of the sample input by the user actually matches the type of the sample module.
The result of the composition and characteristics (temperature, etc.) of the material in the sample may be informed to the user through the machining learning program of claim 20 by comparing the signal pattern extracted from the Ramcell in the device of claim 18 with the pattern of the library of claim 19 . The device of claim 18 may determine whether the type of the sample actually input by the user is correct through the combination of materials in the sample through the library stored therein.
The system according to claim 18, wherein the optical signal library and the machine learning program of claim 19 and 20 are installed on a server and related data transmission/reception system.
The signal pattern transmitted from the device of claim 18, which is stored in the server, and the updated signal pattern in the server may be transmitted to the device of claim 18. Includes transmit/receive systems such as modems.
The module according to claim 18, wherein the user inputs information about the type of sample, temperature, pressure, moisture, direction of polarization, the number of times of optical signal extraction, time between measurements, and the subject of the sample.
In the device of claim 18, the user may input the type of the sample input by the user into the device. For example, a user may enter into the device whether the sample is blood or saliva. In addition, in order to extract a spectrum according to each temperature, pressure, moisture, and direction of polarization, a desired mode and input value can be set by the user. In the mode, input values are automatically changed in a constant pattern or randomly for each temperature, pressure, moisture, and polarization, and a spectrum for each value can be extracted.
By designating the number of times of optical signal extraction for each mode and the time between measurements, it is possible to automatically and repeatedly extract optical signals. By extracting the optical signal for each specific time, the change of the material can be measured. As the number of measurements increases, the relative speed of bonding and separation between substances in equilibrium and the duration of each state can be measured more accurately. The shorter the time difference between measurements, the more accurate the reaction rate between substances over time. measurement is possible. This enables efficient drug extraction and accurate analysis of the reaction between substances.
You can enter information about the subject of the sample. For example, when the sample for analysis is blood, various information about the body from which the blood is extracted and psychological, social, economic, geographical factors related to the subject of the body may also be included. More specifically, information on the subject's age, weight, race, personal or family history, stress level, living location, occupation, income, and the like may be input. The scope of information about the subject of the sample is not limited to that specified in this section. Various substitutions, modifications and changes will be possible by those skilled in the art within the scope not departing from the technical spirit of the present invention described in the claims, and this also falls within the scope of the present invention.
The software and hardware for storing the extracted optical signal, analysis result, big data library, model and information input by the user using the analysis platform according to claim 19 to claim 23 according to claim 19 to claim 23 .
This patent includes all software and hardware technologies that can encrypt personal information to prevent leakage of personal information.
The apparatus of claim 1 for enhancing the flow and mixing of substances in the Ramsel.
A specific electromagnetic field, ultrasound, temperature rise, and vibration can be applied to a Ramcell substrate to enhance the flow and mixing of materials. The increase in temperature can promote convection due to the density difference and increase the kinetic energy of the material. Through the convection phenomenon and increase in kinetic energy, the diffusion movement of materials becomes active, which promotes mixing.
21. Components and mode of operation of the RPU, including the optical signal processing device referred to in claims 8 and 20.
The RPU is a processing unit including either a module for processing optical signal data generated after simultaneously extracting optical signals from multiple Ramcells in parallel or a module for transmitting and receiving.
The RPU may be composed of a module including a light emitter or light emitter, a data processing module that interprets or changes optical signal data, a module that stores memory data such as an optical signal library or other non-memory data, and a module that transmits and receives data. have.
The RPU including the optical signal processing device includes a light emitting module such as the laser module mentioned in claim 20 for optical signal extraction, a photodiode, CCD (aka, charge-coupled device), CMOS (aka, complementary metal oxide semiconductor), PMT ( It is composed of a photodetector such as a so-called photomultiplier tube). It can be composed of a photodetector device that processes optical signals from the light emitting devices of each RPU on a one-to-one basis, and can be configured with a photodetector module that processes the optical signals of each light emitting device at the same time or divides them by time . Such an RPU may include a filter element that absorbs or passes a specific wavelength to implement an optical signal spectrum and imaging, such as a Raman signal.
It is possible to construct a system composed of one diffraction foot among the spectrometer systems that simultaneously extract the optical signals from each Ramcell or extract them by time. The light emitter located at the top of each Ramcell shoots a laser on the Ramcell analysis sample, and the scattered light passes through the beam splitter and lens module, enters the module including the reflective diffraction foot and the reflective mirror, and reflects the scattered light from each Ramcell. and a method in which light is diffusely diffracted by a single reflective diffraction foot through a reflective mirror and enters a photodetector configured in parallel by a reflective mirror configured in parallel.
Imaging of each material can help to distinguish the type and amount of material. To implement imaging, a confocal laser microscope module is included in the RPU. These modules may include a lens that collects light and a pinhole to remove out-of-focus photons. If a pinhole is used, the contrast effect of imaging may be increased but the light intensity may be weakened, so an optoelectronic signal amplifying device such as a PMT is required. Image resolution improvement is usually proportional to the length of the wavelength and inversely proportional to the numerical aperture. Therefore, a laser with a short wavelength and a high numerical aperture are required to extract images of small-sized objects such as biomolecules. Since the destruction of the biosample is possible due to the rather high energy of the photon of a short wavelength, a suitable wavelength can be selected and the movable laser beam mentioned in claim 8 can be utilized. To increase the numerical aperture, the lens design and arrangement can be optimized, or a liquid such as water can be applied to induce the refraction of light between the lens and the object. Depth of focus (aka DoF) can be improved for rapid 3D implementation. There are several ways to achieve this. As an example, it can be implemented using multiple wavelengths, and in order to realize this, it can be composed of laser diodes of various wavelengths. Various microscope modules other than confocal laser microscope module can be used for imaging implementation.
To implement the spectrum, each RPU may include various modules mentioned in claim 8 . However, for miniaturization of the RPU, a device capable of filtering a specific wavelength near each photodetector device without a dispersive Raman spectrometer module using a diffraction grating and pinholes and an interferometer module including a moving mirror It can be installed to extract the spectrum. UV, IR, and visible light filter elements filter only a specific range of wavelengths, and the intensity of light can be sensed through a photodetector that converts filtered photon energy into electronic energy. The selection and arrangement of filters and photodetector elements can be very diverse, but they must be optimized to effectively implement the spectrum through image signal processing (aka, ISP). For example, the IR filter element should be a device that allows photons of IR wavelength or close to IR wavelength to pass and most photons of visible light wavelength do not pass through. It is possible to measure the intensity of IR wavelengths through the photodetector of the IR filter, but it is difficult to determine the intensity and existence of other wavelengths. However, the light that is scattered from the material and reaches a specific IR filter can be a mixture of various wavelengths. In order to extract the spectrum by grasping the overall frequency and intensity of the scattered photons, an algorithm that can be inferred from the data obtained based on a given filter element and photodetector is required. If a UV or visible light filter element is placed near the IR filter element, the combination of photons of UV or visible light wavelength that reached the IR filter element can be inferred through the wavelength band and amount of photons passing through the UV or visible light filter element. can see. This can be inferred from the spatial correlation with the wavelength existing near the IR filter element on the assumption that a normal distribution exists around the axis where the intensity of the light of a specific wavelength generated in a specific area is the largest. In the simplest example, when the type of filter closest to the IR filter is a red filter and a green filter, the wavelength representing the average value of the wavelengths reaching the IR filter is the IR filter and the adjacent red filter and green filter photodetector. By inferring the relative intensity of each IR, red, and green through the intensity of the signal, the wavelength and intensity that can be represented by mixing them can be inferred. In this way, the wavelength and intensity representing the mixing of light reaching each filter can be inferred, and the spectrum of light scattered from the analyte can be obtained based on these values. The spectrum of the light scattered from the analyte is reduced as the number of wavelength ranges used as the filter is diversified, the size of the filter and detector element is small, the filter is uniformly distributed, and the number of times of optical signal detection is increased. can be obtained more accurately. Demosaicing techniques that extract pixel correlations in various images can be used as algorithms.
An optical signal extraction module composed of a single diffraction foot that simultaneously extracts optical signals from each Ramcell or extracts them by time can be configured. The light emitter located at the top of each Ramcell shoots a laser on the Ramcell analysis sample, and the scattered light passes through the beam splitter and lens module, enters the module including the reflective diffraction foot and the reflective mirror, and reflects the scattered light from each Ramcell. and a method in which light is diffusely diffracted by a single reflective diffraction foot through a reflective mirror and enters a photodetector configured in parallel by a reflective mirror configured in parallel.
The RPU may include the spectrum library mentioned in claim 20, a memory and arithmetic unit in which a machine learning program is stored, and a module that can transmit and receive wire or wirelessly to a server or the device of claim 18.
Such an RPU may extract an image or spectrum while one unit or one or more units are fixedly positioned on a specific surface, moved stepwise by a moving module, or moved continuously.
A skin regeneration treatment device using the RPU of claim 26.
By attaching the RPU to the surface of the face, it detects, based on the image and spectrum, that a specific part is lower or higher than the normal part surface due to various wounds or diseases of the face, and a part with a different tissue and color based on the image and spectrum. It is a device that detects the location and treats it through an appropriate RPU laser wavelength so that it becomes close to the surrounding normal surface.
A system for imaging and treating organs in the body comprising the RPU of claim 26 .
By attaching the RPU to the surface of the spherical signal transmission/reception module, images and spectra can be extracted from various angles from organs in the body, and data can be wirelessly transmitted to computers and servers. It is a device that can be injected into an organ in the body, detect abnormal tissue through images and spectrum, and treat it with a laser.
A module for controlling the position and direction of the module including the optical signal extraction module and RPU of claim 8, 20, and 26
As the position and direction of each optical signal extraction module or RPU and the position and direction of the module including them can be finely controlled, the laser is accurately shot on the sample to be analyzed, and optical signals can be efficiently extracted in parallel. have. In addition, each optical signal extraction module and RPU can move stepwise or sequentially in the module containing them.
The claims include modules and methods for moving a substrate including an RPU and for moving an RPU within a substrate. Within the substrate including the RPU, the RPU can be moved up, down, left, and right with respect to the substrate plane, and can be moved up and down for confocal depth aiming. It can also be rotated to allow precise angles of incidence. In order to change the position of the substrate including the RPU, rotation is possible between the RPU substrate and the connected length adjustment module. Rotation is possible in the up, down, left, and right directions between the length adjustment modules connected to each other.

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