WO2022169818A1 - Systèmes et procédés de détection de charges virales en aérosol - Google Patents
Systèmes et procédés de détection de charges virales en aérosol Download PDFInfo
- Publication number
- WO2022169818A1 WO2022169818A1 PCT/US2022/014873 US2022014873W WO2022169818A1 WO 2022169818 A1 WO2022169818 A1 WO 2022169818A1 US 2022014873 W US2022014873 W US 2022014873W WO 2022169818 A1 WO2022169818 A1 WO 2022169818A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- airspace
- viral load
- volume
- frequency
- particles
- Prior art date
Links
- 230000003612 virological effect Effects 0.000 title claims abstract description 93
- 238000000034 method Methods 0.000 title claims description 39
- 230000008569 process Effects 0.000 title claims description 29
- 239000002245 particle Substances 0.000 claims abstract description 127
- 239000000523 sample Substances 0.000 claims abstract description 115
- 241000700605 Viruses Species 0.000 claims abstract description 50
- 239000007788 liquid Substances 0.000 claims abstract description 40
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 22
- 238000001514 detection method Methods 0.000 claims description 17
- 230000004044 response Effects 0.000 claims description 15
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 11
- 239000001569 carbon dioxide Substances 0.000 claims description 11
- 239000013618 particulate matter Substances 0.000 claims description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
- 230000000007 visual effect Effects 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000004891 communication Methods 0.000 claims description 7
- 239000012530 fluid Substances 0.000 claims description 6
- 229940079868 disodium laureth sulfosuccinate Drugs 0.000 claims description 5
- YGAXLGGEEQLLKV-UHFFFAOYSA-L disodium;4-dodecoxy-4-oxo-2-sulfonatobutanoate Chemical compound [Na+].[Na+].CCCCCCCCCCCCOC(=O)CC(C([O-])=O)S([O-])(=O)=O YGAXLGGEEQLLKV-UHFFFAOYSA-L 0.000 claims description 5
- 230000005540 biological transmission Effects 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 244000000022 airborne pathogen Species 0.000 claims description 2
- 239000003570 air Substances 0.000 description 32
- 238000005516 engineering process Methods 0.000 description 30
- 239000000243 solution Substances 0.000 description 26
- 239000000443 aerosol Substances 0.000 description 23
- 238000005070 sampling Methods 0.000 description 13
- 230000007613 environmental effect Effects 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 11
- 239000012080 ambient air Substances 0.000 description 9
- 210000000115 thoracic cavity Anatomy 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 239000012488 sample solution Substances 0.000 description 6
- 238000010200 validation analysis Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- 239000006193 liquid solution Substances 0.000 description 5
- 239000012088 reference solution Substances 0.000 description 5
- 238000004887 air purification Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000000241 respiratory effect Effects 0.000 description 4
- 206010041232 sneezing Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 238000009423 ventilation Methods 0.000 description 3
- 241001678559 COVID-19 virus Species 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101710198474 Spike protein Proteins 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000002019 doping agent Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000007482 viral spreading Effects 0.000 description 2
- 208000035742 Air-borne transmission Diseases 0.000 description 1
- 208000025721 COVID-19 Diseases 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000005557 airborne transmission Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000008358 core component Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000012717 electrostatic precipitator Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940124590 live attenuated vaccine Drugs 0.000 description 1
- 229940023012 live-attenuated vaccine Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/06—Investigating concentration of particle suspensions
- G01N15/0656—Investigating concentration of particle suspensions using electric, e.g. electrostatic methods or magnetic methods
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/22—Devices for withdrawing samples in the gaseous state
- G01N1/2202—Devices for withdrawing samples in the gaseous state involving separation of sample components during sampling
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/22—Devices for withdrawing samples in the gaseous state
- G01N1/2273—Atmospheric sampling
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/06—Investigating concentration of particle suspensions
- G01N2015/0687—Investigating concentration of particle suspensions in solutions, e.g. non volatile residue
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
- G01N27/04—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance
- G01N27/06—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a liquid
Definitions
- COVID-19 and other viruses are spread through airborne transmission. It is known that maintaining good air circulation and low particulate levels within indoor spaces are some of the most effective ways to reduce the risk for humans to become infected by such viruses. Since the beginning of the CO VID-19 pandemic, hundreds of products have been released in the market with the goal of achieving greater indoor air circulation and filtering, based on the assumption that these factors will lead to a virus-free airspace. Virus particles ejected from the human body by sneezing and exhaling, however, can have a relatively high velocity that makes it difficult to efficiently and effectively remove all of the particles from an indoor air space. Thus, no air circulation system or air filtration system can protect human for airborne viruses and other pathogens with absolute efficacy and reliability. And chemical or ion-based air purification systems can present logistical and safety-related challenges, because these types of systems can be harmful to human health and thus can be used only when humans are not present.
- the disclosed technology relates to systems and processes for detecting airborne virus loads.
- the technology addresses drawbacks of present air purification systems by accurately determining whether a space contains a detectable level of virus particles, thereby helping to identify the location and origin of an infection or potential infection.
- the systems and techniques also can be used to determine whether an air purification system is working effectively, by continually checking whether the airborne viral load in a space decreases following the sudden introduction of a virus into the space caused by the entrance of an infected person.
- an Internet of Things (loT) based system such as that disclosed herein can be used to inform occupants throughout a building or other living space whether any part of the building or living space is sensing a higher viral load, and thus can act both as a locator of virus-spreading sources, and a warning system. Even if no air filtering or purification system is present in a particular space, which is common in public gatherings, the detection of viral loads by the disclosed system can be highly useful information because it can identify the need to disperse the gathering for safety- related reasons.
- LoT Internet of Things
- a system for detecting the presence of a virus in an airspace includes a first volume of a liquid, the first volume having particles sampled from the airspace absorbed therein; a second volume of the liquid; and a first and a second conductivity probe.
- the system also includes a first frequency generator communicatively coupled to the first conductivity probe and configured to, during operation, apply a first alternating voltage to the first conductivity probe while the first conductivity probe is immersed at least in part in the first volume, the first alternating voltage causing a first alternating current to flow between the first conductivity probe and the first frequency generator;
- the system further includes a second frequency generator communicatively coupled to the second conductivity probe and configured to, during operation, apply a second alternating voltage to the second conductivity probe while the second conductivity probe is immersed at least in part in the second volume, the second alternating voltage causing a second alternating current to flow between the second conductivity probe and the second frequency generator;
- the system also includes a differential frequency detector communicatively coupled to the first and second frequency generators and configured to, during operation, determine a difference between the frequencies of the first and second alternating currents; and a computing device communicatively coupled to the differential frequency detector and configured to, during operation, determine a viral load in the first volume based on the difference between the frequencies of the first and second alternating currents.
- the second volume of the liquid is free of virus particles.
- the liquid has the characteristic of becoming polarized in the presence of a virus.
- the first frequency generator is further configured to, during operation, generate a first output representing the first alternating current;
- the second frequency generator is further configured to, during operation, generate a second output representing the first alternating current;
- the differential frequency detector is further configured to, during operation, determine the difference between the frequencies of the first and second alternating currents based on the first and second outputs.
- the first and second conductivity probes each include a first and a second electrode.
- the computing device is further configured to correlate the viral load in the first volume with a viral load in the airspace.
- the computing device is further configured to generate and send a notification when the viral load in the airspace is determined to be greater than a predetermined value.
- the system further includes a visual altering device communicatively coupled to the computing device. The computing device is further configured to generate an output when the viral load in the airspace is determined to be greater than a predetermined value; and the visual alerting device is configured to generate a visual alert in response to the output of the computing device.
- the system further includes an audible altering device communicatively coupled to the computing device.
- the computing device is further configured to generate an output when the viral load in the airspace is determined to be greater than a predetermined value; and the audible alerting device is configured to generate an audible alert in response to the output of the computing device.
- the computing device is an edge-cloud server.
- the system further includes a particle collector in fluid communication with the airspace and configured to, during operation, separate the particles from a sample of the airspace.
- the particle collector includes a coarse filter configured to remove from the sample of the airspace particles having a size greater than a predetermined value.
- the coarse filter is configured to remove from the sample of the airspace particles having an aerodynamic diameter greater than about ten microns.
- the particle collector further includes a particle separator configured to remove from the sample of the airspace the particles sampled from the airspace.
- system further includes a fan in fluid communication with the particle collector and configured to, during operation, direct the sample the airspace from the airspace to the particle collector.
- the liquid includes one of deionized water, distilled water, isopropyl alcohol, and disodium laureth sulfosuccinate solution.
- the differential frequency detector is configured to, during operation, determine the difference between the frequencies of the first and second alternating currents using one of a homodyne and a heterodyne detection technique.
- a process for detecting the presence of a virus in an airspace includes providing a first volume of a liquid, the first volume having particles sampled from the airspace absorbed therein; providing a second volume of the liquid; immersing a least a portion of a first conductivity probe in the first volume; and immersing a least a portion of a second conductivity probe in the second volume.
- the process further includes applying an alternating voltage to the first probe and the second probe; determining a difference between: a frequency of an alternating current produced in the first electrode in response to the application of the alternating voltage to the first electrode, and a frequency of an alternating current produced in the second electrode in response to the application of the alternating voltage to the second electrode; and determining a viral load in the first volume based on the frequency difference.
- the process further incudes maintaining the first and second volumes at substantially the same temperature.
- the process further includes correlating the viral load in the first volume with a viral load in the airspace.
- determining a difference between: a frequency of an alternating current produced in the first electrode in response to the application of the alternating voltage to the first electrode, and a frequency of an alternating current produced in the second electrode in response to the application of the alternating voltage to the second electrode includes determining the frequency difference using a homodyne detection technique.
- the process further includes generating and sending a notification when the viral load in the airspace is determined to be greater than a predetermined value.
- the process further includes removing from a sample of the airspace particles having a size greater than a predetermined value.
- the process further includes removing from the sample of the airspace the particles sampled from the airspace.
- determining a viral load in the first volume based on the frequency difference includes determining the viral load in the first volume based on the frequency difference using an edge-cloud server.
- determining a viral load in the first volume based on the frequency difference includes determining the viral load in the first volume based on a predetermined relationship between the viral load in the first volume and the frequency difference.
- the process further includes calculating a minimum separation distance needed to reduce a potential for human-to-human transmission of airborne pathogens, based on an estimate of distance the particles will travel upon being exhaled as determined using the temperature and relative humidity of the airspace, and the particle concentration in the airspace.
- the process further includes validating the determination of the viral load based at least in part on a carbon dioxide level, a particulate matter level, and the presence or absence of people in the airspace.
- FIG. l is a block diagram of a system for detecting aerosolized viral loads.
- FIG. 2 is a flow chart depicting operation of the system shown in FIG. 1.
- FIG. 3 A is a diagrammatic illustration of a coarse filter of a particle collector of the system shown in FIG. 1.
- FIG. 3B is a diagrammatic illustration of an alternative embodiment of the coarse filter shown in FIG. 3 A.
- FIG. 4A is a diagrammatic illustration of an aerosol sampler the particle collector of the system shown in FIG. 1.
- FIG. 4B is a diagrammatic illustration of an alternative embodiment of the aerosol sampler shown in FIG. 4A.
- FIG. 4C is a diagrammatic illustration of another alternative embodiment of the aerosol sampler shown in FIG. 4A.
- FIG. 4D is a diagrammatic illustration of another alternative embodiment of the aerosol sampler shown in FIG. 4A.
- FIG. 4E is a diagrammatic illustration of another alternative embodiment of the aerosol sampler shown in FIG. 4A.
- FIG. 5 is a diagrammatic illustration of various electrical components of the system shown in FIG. 1, with a graphical representation of various frequency measurements made using the components.
- FIG. 6A is a graph depicting the relationship between the frequency of an alternating current through a first conductivity probe of an embodiment of the system shown in FIG. 1, as a function of the viral load in a solution in which the probe is immersed.
- FIG. 6B is a graph depicting the difference between the alternating current frequency depicted in FIG. 6A, and the frequency of an alternating current through a second conductivity probe immersed in a solution that does not contain a viral load, as a function of the viral load in which the first probe is immersed.
- inventive concepts are described with reference to the attached figures, wherein like reference numerals represent like parts and assemblies throughout the several views.
- the figures are not drawn to scale and are provided merely to illustrate the instant inventive concepts.
- the figures do not limit the scope of the present disclosure or the appended claims.
- Several aspects of the inventive concepts are described below with reference to example applications for illustration. It should be understood that numerous specific details, relationships, and methods are set forth to provide a full understanding of the inventive concepts.
- inventive concepts can be practiced without one or more of the specific details or with other methods. In other instances, well- known structures or operation are not shown in detail to avoid obscuring the inventive concepts.
- FIGS. 1 and 3-5 disclose a system 10 for detecting an airborne virus load.
- the system 10 uses alternating current (AC) conductivity measurement to determine the viral load in a liquid medium into which particulate matter sampled from the monitored spaced has been introduced.
- the system 10 also uses a reference solution that is maintained at substantially the same environmental conditions as the solution containing the sampled particles, and does not include any virus particles.
- AC alternating current
- An alternating voltage is applied across the electrodes of a first probe immersed in the sample solution, i.e., the solution into which the sampled particulate matter has been introduced.
- a substantially identical alternating voltage is applied across the electrodes of a second probe immersed in the reference solution.
- the voltage potential across the electrodes of the first and second probes causes an alternating current to flow through each probe.
- the difference between the frequencies of the respective alternating currents is determined using a homodyne detection technique. In alternative embodiments, the difference between the frequencies of the respective alternating currents is determined using a heterodyne detection technique.
- the difference in frequency can be used to estimate the viral concentration, including very low viral concentrations, in the sample solution.
- the presence of a viral load in the sample solution affects the electrochemical characteristics of the solution, which in turn affects the electrical conductivity and dielectric properties of the solution.
- the change in electrical conductivity and dielectric properties affect the frequency of the alternating current passing between the electrodes of the probe immersed the sample solution by a very small, but detectable, amount.
- the difference between the frequency response of the alternating currents in the probes immersed in the sample and reference solutions thus can be correlated to the presence and magnitude of the viral load in the reference solution.
- the system 10 has been shown to be sensitive enough to detect small viral loads in the range of 10-50 particle/100 mL of air with a high degree of reliability and repeatability.
- the system 10 can be characterized as including, without limitation, three core component groups: an aerosol classification and bio-sampling group; a viral detection group that detects the presence and magnitude of a viral load based on changes in electrical properties of the liquid in which viral particles are suspended; and an edge computation and loT platform group that facilitates validation of the acquired data, and generation of notifications and warnings when an airborne virus is detected.
- an aerosol classification and bio-sampling group a viral detection group that detects the presence and magnitude of a viral load based on changes in electrical properties of the liquid in which viral particles are suspended
- an edge computation and loT platform group that facilitates validation of the acquired data, and generation of notifications and warnings when an airborne virus is detected.
- air quality In aerosol sampling, air quality generally is determined by: (i) determining the density of airborne particles of different sizes; (ii) determining the “health” of breathing space, i.e., whether the breathing space is too densely populated, and (iii) determining the air properties to scientifically calculate the air transport characteristics.
- FIGS. 2 are 2B are a flow chart depicting operation of the system 10. The initial portion of the virus detection process performed by the system 10 comprises collecting air from throughout the room or other space in which the air quality is to be monitored; and isolating particles that potentially are the most conductive to causing an infection and spreading the virus.
- a person infected with a respiratory virus typically emits a variety of aerosols that can be classified in accordance with their aerodynamic diameter.
- the aerodynamic diameter of a particle is defined as the diameter of a sphere of density lg/cm 3 which suspends or settles in still air at same velocity as the particle.
- An infected person in general, can emit aerosolized particles having aerodynamic diameters in the range of 1 micron to 200 microns.
- the particles having an aerodynamic diameter greater than 100 microns are much less likely to remain airborne than smaller diameter particles, and settle to the nearby ground very quickly after being emitted. Such particles, therefore, are highly unlikely to cause virus spread.
- Aerosolized particles having an aerodynamic diameter in the range of ten microns to 100 microns are characterized as inhalable fractions. Such particles typically become trapped in the nose and mouth, and therefore are unlikely to cause an infection by way of the respiratory system.
- Aerosolized particles with an aerodynamic diameter in the range of four microns to ten microns are characterized as thoracic fractions. These type of particles readily can reach the throat and upper respiratory duct, and therefore are likely to result in infection and spreading of the virus.
- Aerosolized particles having an aerodynamic diameter less than four microns are characterized as respirable fractions. These types of particle generally are considered the most dangerous, because such particles can reach the finest parts of the lungs. Respirable particles, therefore, are responsible to a large extent for the spread of illnesses due to airborne viral pathogens.
- Thoracic and respirable particles are believed to make up a major portion of the viral load in a typical space in which the COVID-19 virus is spread. And as noted above, these types of particles, if inhaled, are highly likely to cause an infection.
- the system 10 is configured to target thoracic and respirable particles when estimating the viral load, to help maximize the detection of potentially infectious particles, and decrease false readings based on the detection of larger particles.
- the system 10 comprises a fan 22, depicted schematically in FIG. 1.
- the fan 22 is configured to draw ambient air from the space or volume of air being monitored for a viral load (step 100 in FIG. 2A).
- the fan 22 can be configured to generate a suction that draws air from every direction around the fan 22, and from a distance of up to 12 feet away from the fan 22, to help maximize the area of coverage and the operational efficiency of the system 10.
- the fan 22 is communicatively coupled to a controller 23 of the system 10, as shown in FIG. 1.
- the controller 23 is configured activate and deactivate the fan 22 at the start and end of each sampling period.
- Each sampling period can have a duration of, for example, about ten to about 100 seconds.
- the controller 23 can be configured to obtain a sample at predetermined intervals, such as about every one to ten minutes.
- the system 10 can be configured so that the sampling period and sampling intervals can be varied by the user via inputs provided through a suitable input device communicatively coupled to the controller 23.
- the system 10 can be further configured so that the user can initiate a sampling period on demand, by entering a command though the input device.
- the input device can be, for example, a smart phone 54, a desktop computer 56, a server, such as edge-cloud server 46, etc., equipped with a suitable application and communicatively coupled to the controller 23 as discussed below.
- the smart phone 54, desktop computer 56, and edge-cloud server 46 are shown in FIG. 1.
- the controller 23 can be any type of computing device capable of performing the logical operations described therein.
- the controller 23 can be a microcontroller comprising, in relevant part, a microprocessor; a memory communicatively coupled to the microprocessor; and computer executable instructions stored in the memory.
- the computer executable instructions are configured so that, upon execution by the microprocessor, the computer executable instructions cause the microcontroller to perform the logical operations disclosed herein.
- the system further comprises a particle collector 24, depicted schematically in FIG. 1.
- the particle collector 24 is in fluid communication with the fan 22, and is located downstream from the fan 22 so that the particle collector 24 receives the ambient air entrained by the fan 22.
- the particle collector 24 is configured to collect aerosolized virus particles likely to result in an infection, and to separate and eliminate aerosolized particles of no interest, i.e., particles that are unlikely to result in infection.
- the particle collector 24 comprises a coarse filter that filters out, or eliminates particles having an aerodynamic diameter greater than about ten microns (step 102 in FIG. 2A).
- virus particles characterized as inhalable fractions i.e., particles with an aerodynamic diameter greater than ten microns
- the coarse filter can use any suitable technique to eliminate the inhalable fractions.
- the coarse filter can comprise a filter mesh 26, shown in FIG. 3 A, that captures particles larger than ten microns.
- the coarse filter can comprises a cyclonic filter 27, shown in FIG. 3B. having a cut-off particle diameter of ten microns.
- the particle collector 24 further comprises an aerosol sampler.
- the air sample is directed to the aerosol sampler following removal of the inhalable fractions in the coarse filter.
- the aerosol sampler is configured to separate the thoracic and respirable fractions from the air flow after the larger particles have been removed by the coarse air filter (step 102 in FIG. 2A).
- the aerosol sampler can use any suitable technique to perform this function.
- the aerosol sampler can comprise an impinger 70 configured to capture aerosolized particles having an aerodynamic diameter of less than ten microns.
- the aerosol sampler can comprise a cyclonic filter 72 configured to capture aerosolized particles having an aerodynamic diameter of less than ten microns.
- the aerosol sampler can comprise a condensation-based separator 74 configured to introduce steam into the sampled airflow.
- the resulting condensation of causes aerosolized particles having an aerodynamic diameter of less than ten microns to drop out of the airflow.
- the aerosol sampler can comprise an impactor 76 configured to capture aerosolized particles having an aerodynamic diameter of less than ten microns.
- the aerosol sampler can comprise an electrostatic precipitator 78 configured to capture aerosolized particles having an aerodynamic diameter of less than ten microns.
- the aerosol sampler is configured so that the thoracic and respirable fractions, upon being separated from the air stream, drop into, and become suspended in a liquid solution positioned beneath the aerosol sampler as shown in FIGS. 4A-4E (step 106 I FIOG. 2A).
- the sampled air from which the thoracic and respirable fractions have been separated is released back in the ambient environment to complete the bio sampling process.
- the liquid into which the virus particles are dropped acts as a base of a colloidal solution in which the particles are absorbed.
- the liquid can be any of deionized water, distilled water, isopropyl alcohol, disodium laureth sulfosuccinate (DLS) solution, and other types of liquids that become polarized upon the absorption of virus particles.
- DLS disodium laureth sulfosuccinate
- the absorption of viral particles into the liquid changes the electrochemical properties of the liquid; and the presence of virus particles can be detected by measuring the change in electrical properties of the liquid. This in turn can facilitate the determination an airborne viral load in the space from which the particles were obtained.
- the electrochemical properties of a liquid also are dependent on handling, i.e., shaking, which can result in vibrations that produce more electrostatic charge separation of the virus particles.
- the electrochemical properties of a liquid also are dependent on environmental factors such as the temperature of the liquid. Therefore, to eliminate ambiguous or erroneous results due to changes in temperature and other environmental factors, the system 10 uses a two-chamber analysis technique in which one liquid-filled chamber is used as a reference, and the other liquid- filled chamber contains a colloidal solution of entrapped sampled particles. More specifically, the system 10 further comprises a reference chamber 30, and a sample chamber 32, as shown in
- the thoracic and respirable fractions upon being separated from the air sample in the aerosol sampler, are absorbed into a liquid solution. Upon completion of the predetermined sampling period, this solution is transferred to the sample chamber 32.
- the reference chamber 30 contains the same liquid composition, in the same volume, as the sample chamber 32, but the liquid composition in the reference chamber 30 does not include any absorbed particles.
- the liquid composition in the sample chamber 30 otherwise is substantially identical to the liquid composition in the sample chamber 32.
- the liquid composition in the reference chamber 30 is maintained at substantially the same environmental conditions, including temperature, as the liquid composition in the sample chamber 32.
- the relevant properties of the liquid composition in the reference chamber 30, therefore, can act as a baseline against which changes of the conductivity of the solution in the sample chamber 32 can be evaluated. As discussed below, this technique helps to maximize the signal to noise ratio in the signal that ultimately is used to indicate of the viral load in the sample chamber 32.
- the system 10 further includes a two-probe/four-electrode system to measure the relevant characteristic of the solutions in the reference chamber 30 and the sample chamber 32. More specifically, referring to FIG. 12, the system 10 comprises a first conductivity probe 36 and an identical second conductivity probe 38, shown in FIGS. 1 and 5. The first conductivity probe 36 is suspended in the solution in the sample chamber 32. The second conductivity probe 38 is suspended in the solution in the reference chamber 30. The first conductivity probe 36 and the second conductivity probe 38 each include a positive electrode 39a and a negative electrode 39b.
- the system 10 also comprises a first alternating frequency generator 40, a second frequency generator 41, and a differential frequency detector 42, also shown in FIGS. 1 and 5.
- the first frequency generator 40 is communicatively coupled to the first probe 36, and to the differential frequency detector 42.
- the second frequency generator 41 is communicatively coupled to the second probe 38, and to the differential frequency detector 42.
- the first and second frequency generators 40, 41 each generate a sinusoidally-varying voltage that produces an alternating electrical potential across the positive and negative electrodes 39a, 39b of the respective first and second conductivity probe 36, 38 (activities 108a, 108b in FIG. 2A).
- the frequency of the voltage is characteristic of the RC (resistance/capacitance) of the alternating current (AC) circuit driving the alternating voltages.
- the electrical potential across the positive and negative electrodes 39a, 39b causes an alternating current to flow between the positive and negative electrodes 39a, 39b, via the solution in which the first and second electrodes 39a, 39b are immersed.
- the frequency of the alternating current is related to the electrical conductivity of the solution.
- the liquid solution in the sample chamber 32 becomes polarized upon the absorption of virus particles, such a CO VID-19 virus particles, that have spike proteins, since the presence of the spike proteins results in an electrostatic charge.
- the electrical conductivity of the solution is related to the presence or absence of virus particles in the sample chamber 32.
- the first and second frequency generators sources 40, 41 each produce a sinusoidal output signal having a frequency approximately equal to the frequency of the alternating current flowing through the respective first and second probes 36, 38.
- the output signals are transmitted to the differential frequency detector 42.
- the differential frequency detector 42 determines the frequency difference between the signals using a homodyne detection technique (step 110 in FIG. 2A).
- the differential frequency detector 42 can determine the frequency difference using a heterodyne detection technique, in alternative embodiments.
- the differential frequency detector 42 generates an output representative of the frequency difference, and sends the output to the controller 23.
- the differential frequency detector 42, the first and second frequency generators 40, 41, and the first and second probes 36, 38 thus constitute a homodyne frequency detection circuit.
- the frequency difference is processed to estimate the amount of virus particles in the solution within the sample chamber 32.
- the frequency of the alternating current flowing between the first and second probes 36, 38 and the respective first and second alternating frequency generators 40, 41 is related to the conductivity of the liquid solution which the first or second probe 36, 38 is immersed; and the conductivity of the solution is related to the presence or absence of virus particles in the solution.
- the frequency of the output signal generated by the first alternating frequency generator 40 therefore, is related to the amount of virus particles in the solution within the sample chamber 32.
- the solution in the reference chamber 30 is substantially free of virus particles, and is maintained at substantially the same environmental conditions as the solution in the sample chamber 32.
- the frequency of the output signal generated by the second frequency generator 41 therefore, represents a baseline reference against which the effects of the any virus particles in the sample chamber 32 can be evaluated.
- the output signal generated by the differential frequency detector 42 is transmitted to the controller 23.
- the output signal is processed to determine the presence, and amount of viral load in the solution within the sample chamber 32.
- the frequency difference between the respective current through the first and second probes 36, 38, as determined by the differential frequency detector 42 is correlated with a predetermined relationship between the viral load and the frequency difference (step 112 in FIG. 2A).
- the predetermined relationship is generated by a calibration process in which the frequency difference is evaluated in the presence of varying amounts of virus particles in the sample chamber 32.
- the viral load in the sample chamber 32 is correlated with the amount of thoracic and respirable particles in the airspace from with the sampled particles were obtained, to provide a determination of the presence, and magnitude of the viral load in the airspace (step 114).
- the presence, and greater amount of viral particles in the sample chamber 32, in relation to the reference chamber 30, i.e., the baseline condition without virus particles, generates a polarization of the liquid in the sample chamber 32 that is proportional to the number of virus particles absorbed in the liquid in the sample chamber 32.
- the characteristic frequency of the liquid in the sample chamber 32 changes monotonically with the virus load in the air from which the particles in the sample chamber 32 have been sampled.
- the calculation of the viral load in the sample chamber 32, and the determination of the presence and magnitude of the viral load in the sampled airspace, can be performed by the edgecloud server 46.
- the edge-cloud server 46 is communicatively coupled to the controller 23 by way of a wireless gateway 52 or other suitable means.
- the calculation of the viral load in the sample chamber 32, and the determination of the presence and magnitude of the viral load in the sampled airspace can be performed by other types of computing devices including, without limitation, the controller 23 itself.
- the results of the air-sample analysis i.e., viral load in the sampled airspace
- a validation process discussed below (step 116 in FIG. 2A). If the results are deemed valid, the results of the air-sample analysis, and other environmental data, can be transmitted to, and displayed and/or stored on one or more display or storage devices (step 118).
- the system 10 can include a visual display 51 communicatively coupled to the controller 23 by a wired or wireless means.
- the viral load determined by the system 10 can be displayed on the display 51.
- Environmental data such as the ambient CO2 level, PM concentration, air temperature, and relative humidity also can be displayed.
- Other information such as a plot of the airborne viral load over time, also can be displayed. If the viral load is above a safe level, a warning message, such as “High Viral Load Detected. Please Use Proper Safety Precautions and Air Purification” also can be displayed.
- the wireless gateway 52 is communicatively coupled to the controller 23, and facilitates communication between the controller 23, the edge-cloud server 46, and other devices on which the air-sampling results, environmental data, and warnings can be displayed, processed, and/or stored.
- the above noted information displayed on the display 51 also can be displayed on the smart phone 54 or the desktop computer 56.
- data can be further processed and/or stored on a local server or a cloud server (not shown).
- Communication between the wireless gateway 52 and the above-noted devices can be facilitated by any suitable means, such as the internet, a cellular network, Wi-Fi, a local area network, a wide area network,
- the system 10 can be further configured so that, upon the detection of a high viral load, the system 10 immediately generates warnings and notifications cautioning recipients to take adequate precautions, such as leaving the area, to reduce the potential for viral exposure and possible infection (step 120 of FIG. 2 A).
- the system 10 can be configured to send such warnings and notifications to pre-designated recipients by way of e-mail or text messaging.
- the pre-designated recipients can include the normal occupants of a particular floor of an office building on which the system 10 is used to monitor air quality.
- the system 10 also can be configured so that, upon the detection of a high viral load, the system 10 generates a command that activates an air filtration, disinfection, or ventilation system (not shown) that services the airspace in which the viral load have been detected (step 122).
- the system 10 further can include a visual alerting device in the form of one or more LED displays 58, shown in FIG. 1.
- the LED displays 58 are communicatively coupled to the edge-cloud server 46, and can be placed in locations where they can be seen easily by occupants within the space being monitored by the system 10.
- the LED displays 58 Upon receiving an input from the edgecloud server 46 that a high viral load or other alarming condition exists, the LED displays 58 illuminates, thereby providing a visual indication to those in the vicinity of the LED displays 58 that the viral load in the local space is at, or is approaching an unsafe level (step 124).
- the system 10 further can include an audible alerting device in the form of one or more buzzers 60, depicted in FIG. 1.
- the buzzers 60 are communicatively coupled to the edge-cloud server 46, and can be placed in locations where they can be heard easily by occupants within the space being monitored by the system 10.
- the buzzers 60 Upon receiving an input from the edge-cloud server 46, that a high viral load or other alarming condition exists, the buzzers 60 emit an audible sound such as a pulsing buzzing noise, thereby providing an audible indication to those in the vicinity of the buzzers 60 that the viral load in the local space is at, or is approaching an unsafe level (step 126).
- An embodiment of the system 10 was tested with different polar and non-polar dopants with distilled water.
- the frequency of the respective AC currents passing through the probes immersed in the sample and reference solutions was recorded with every viral dosage.
- the virus selected for the testing was a live attenuated MMR (measles, mumps and rubella) vaccine, at a concentration of 140 viral particles per 10 pL.
- Fig. 6A the frequency of the output of the sample probe increased linearly as the viral load was increased.
- Fig. 6B the difference between the output frequencies of the sample probe and the reference probe likewise increased linearly as the viral load was increased.
- the testing also was conducted using polio and rotavirus live attenuated vaccines; and similar frequency responses were found using these viruses.
- each type of virus particle will generate different level of Zeta potential and Debye radius. Therefore, the system 10 relies on an advanced adaptive signal processing technique of comparing the response of the sample probe with a time series of baseline data to predict whether there is a burst of viral activities in the monitored airspace.
- the validation process can be performed using a validation algorithm stored on, and executed by the edge-cloud server 46.
- the validation algorithm can be stored on and executed by a different computing device, such as the controller 23, in alternative embodiments.
- the validation process is based on inputs such as the carbon dioxide (CO2) level in the space from which the sample was obtained; the particulate matter (PM) concentration and distribution within the space; and the presence or absence of people in the space.
- CO2 carbon dioxide
- PM particulate matter
- the carbon dioxide concentration and the particulate matter concentration can be obtained from a respective carbon dioxide sensor 62 and particulate matter sensor 64.
- the presence and/or number of persons in the space can be evaluated based on inputs from one or more proximity sensors or motion detectors 86.
- the carbon dioxide sensor 62, particulate matter sensor 64, and proximity sensors or motion detectors 86 can be communicatively coupled to the edge cloud server 46 by way of the wireless gateway 52, as illustrated in FIG. 1.
- the CO2 level, PM concentration, and the presence or absence of people are factors that can indicate the likelihood that an airborne virus is present in a particular space.
- a relatively low level of carbon dioxide e.g., about 400 ppm or less
- a relatively low particulate level e.g., about ten ug/m 3 (micro grams per cubic meter) or less
- ten ug/m 3 micro grams per cubic meter
- the absence of any people in the space likewise is interpreted an indication that the likelihood of a significant viral load in the space is low.
- the system 10 generates an output indicating an unacceptably high viral load under such circumstances, the output is interpreted as a false positive, i.e., the result is considered invalid. The suspect result can be ignored, and if desired, the user can initiate another sampling cycle.
- a relatively high level of carbon dioxide e.g., about 420 to about 450 ppm or greater
- a relatively high particulate level e.g., about 50 ug/m 3 to about 100 ug/m 3 or greater
- the system 10 generates an output indicating an acceptably low viral load under such circumstances, the output is interpreted as a false negative, i.e., the result is considered invalid.
- the suspect result can be ignored, and if desired, the user can initiate another sampling cycle.
- the edge-cloud server 46 can be configured to determine the minimum social distance, based on the environmental conditions in the space being monitored.
- the edgecloud server 46 can be programmed with algorithms that, when executed by the edge-cloud server 46, calculate the minimal social distance at a given time based on the measured temperature and humidity of the ambient air; and the concentration and size distribution of particles in the ambient air.
- the size of the droplet nuclei resulting from sneezing, coughing, and talking is a function of the process by which the droplets are generated, and the environmental conditions. For example, sneezing can generate around 40,000 droplets in the 0.5 micron to 12 micron range, which most likely are aerosolized. Also, studies have shown that talking for five minutes can generate the same number of droplet nuclei as a cough, i.e., about 3,000 droplet nuclei. The actual size distribution of the droplets is dependent on parameters such as the exhaled air velocity, the viscosity of the fluid, and the flow path.
- the time of flight and distance traveled by exhaled particles depend upon the transport characteristics of the ambient air, i.e., the viscosity, temperature, specific heat capacity, and thermal conductivity of the ambient air.
- the transport characteristics vary with the ambient temperature and relative humidity, and hence can change the minimum social distance required to minimize the potential for person-to-person transmission of pathogens carried by exhaled particles.
- the following set of equations can be used to estimate the distance an exhaled particle will travel, using the temperature and relative humidity of the air through which the particle will travel, and the concentration of particles in the air:
- the above equation set can be used to estimate the minimum social distance based on the ambient temperature and relative humidity, and the particle concentration in the ambient air.
- the edge-cloud server 46 is configured to perform a Runge Kutta Fourth Order Method to solve the above differential equations for the distance traveled by the droplet under the specific conditions existing at a particular time.
- the distance traveled by the droplet represents the minimum separation distance for that particular point in time.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- Immunology (AREA)
- General Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Dispersion Chemistry (AREA)
- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
Abstract
L'invention concerne des systèmes de détection de charges virales en aérosol dans un espace aérien comprenant un premier et un deuxième volume d'un liquide. Le premier volume comprend des particules échantillonnées dans l'espace aérien, et le deuxième volume est exempt de particules virales. Une première sonde de conductivité est immergée dans le premier liquide, et une deuxième sonde de conductivité est immergée dans le deuxième liquide. Un courant alternatif est appliqué à chacune des première et deuxième sondes de conductivité. La différence entre les courants alternatifs résultants traversant les première et deuxième sondes de conductivité est déterminée, et est utilisée pour estimer la charge virale dans le premier volume, et dans l'espace aérien.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN202121004520 | 2021-02-02 | ||
IN202121004520 | 2021-02-02 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022169818A1 true WO2022169818A1 (fr) | 2022-08-11 |
Family
ID=82741652
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2022/014873 WO2022169818A1 (fr) | 2021-02-02 | 2022-02-02 | Systèmes et procédés de détection de charges virales en aérosol |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2022169818A1 (fr) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4288544A (en) * | 1978-08-23 | 1981-09-08 | Kyowa Hakko Kogyo Co., Ltd. | Method and apparatus for measuring microorganism activity |
US20030186351A1 (en) * | 2000-03-17 | 2003-10-02 | Katsuhiko Machida | Drug susceptibility measurement method and apparatus thereof |
US20040239344A1 (en) * | 2001-08-09 | 2004-12-02 | Shenggen Hu | Method and apparatus for detecting extraneous matter in a fluid |
US20120252003A1 (en) * | 2011-03-30 | 2012-10-04 | United State of America, as Represented by the Secretary of the Navy | Bacteria Identification by Phage Induced Impedance Fluctuation Analysis |
US10327692B2 (en) * | 2013-08-06 | 2019-06-25 | Tanita Corporation | Apparatus for assessing muscle quality |
-
2022
- 2022-02-02 WO PCT/US2022/014873 patent/WO2022169818A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4288544A (en) * | 1978-08-23 | 1981-09-08 | Kyowa Hakko Kogyo Co., Ltd. | Method and apparatus for measuring microorganism activity |
US20030186351A1 (en) * | 2000-03-17 | 2003-10-02 | Katsuhiko Machida | Drug susceptibility measurement method and apparatus thereof |
US20040239344A1 (en) * | 2001-08-09 | 2004-12-02 | Shenggen Hu | Method and apparatus for detecting extraneous matter in a fluid |
US20120252003A1 (en) * | 2011-03-30 | 2012-10-04 | United State of America, as Represented by the Secretary of the Navy | Bacteria Identification by Phage Induced Impedance Fluctuation Analysis |
US10327692B2 (en) * | 2013-08-06 | 2019-06-25 | Tanita Corporation | Apparatus for assessing muscle quality |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20220196268A1 (en) | Air sensing and purification systems | |
WO2022047340A1 (fr) | Systèmes de détection et de purification d'air | |
EP2370802B1 (fr) | Capteur destiné à détecter des particules en suspension dans l'air | |
Dudalski et al. | Experimental investigation of far‐field human cough airflows from healthy and influenza‐infected subjects | |
JP5388846B2 (ja) | 粒度および蛍光の同時測定による病原体検出 | |
JP5877529B2 (ja) | エアロゾルの検出 | |
EP2244236A1 (fr) | Détecteur de fumée aspirant à vitesse d'air variable | |
Buonanno et al. | Metrological performances of a diffusion charger particle counter for personal monitoring | |
US20230152199A1 (en) | Systems and processes for detecting aerosolized viral loads | |
WO2017181955A1 (fr) | Dispositif de détection de concentration de poussière et procédé de détection de concentration de poussière | |
CN109632589A (zh) | 一种大气颗粒物检测装置和方法 | |
Occhipinti et al. | Particulate matter monitoring: Past, present and future | |
WO2022169818A1 (fr) | Systèmes et procédés de détection de charges virales en aérosol | |
WO2022115755A1 (fr) | Systèmes et procédés de détection de charges virales en aérosol | |
JP5657552B2 (ja) | 気流中の荷電浮遊粒子の粒度分布の経時的進展を特徴付けるための装置 | |
CN206114476U (zh) | 一种测量细颗粒物浓度的传感器 | |
Kim et al. | Electrochemical detection of airborne influenza virus using air sampling system | |
US20230408121A1 (en) | Systems and processes for detecting aerosolized viral loads | |
KR101854986B1 (ko) | 나노입자 분석방법 및 이의 시스템 | |
Brown et al. | PRELIMINARY ASSESSMENT OF A DEVICE FOR PASSIVE SAMPLING OF AIRBORNE PARTICIPATE | |
Penner et al. | Generation, characterization, and comparison of human exhaled and technical aerosols for the evaluation of different air-purifying technologies against infectious aerosols | |
Zhou et al. | Airborne particles detection and sizing at single particle level by a novel electrical current pulse sensor | |
Urban et al. | Measurement of smoke particle size under low-gravity conditions | |
CN105203439A (zh) | 空气净化控制方法及装置 | |
Beamer et al. | Comparison of capture efficiencies measured by tracer gas and aerosol tracer techniques |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22750289 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 22750289 Country of ref document: EP Kind code of ref document: A1 |