WO2022246087A1 - High-throughput real time bio-threat screening - Google Patents
High-throughput real time bio-threat screening Download PDFInfo
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- WO2022246087A1 WO2022246087A1 PCT/US2022/030071 US2022030071W WO2022246087A1 WO 2022246087 A1 WO2022246087 A1 WO 2022246087A1 US 2022030071 W US2022030071 W US 2022030071W WO 2022246087 A1 WO2022246087 A1 WO 2022246087A1
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Classifications
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- 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
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
- G01N33/5438—Electrodes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
- A61B5/1477—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means non-invasive
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4866—Evaluating metabolism
-
- 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
- G01N33/0004—Gaseous mixtures, e.g. polluted air
- G01N33/0009—General constructional details of gas analysers, e.g. portable test equipment
- G01N33/0027—General constructional details of gas analysers, e.g. portable test equipment concerning the detector
- G01N33/0036—General constructional details of gas analysers, e.g. portable test equipment concerning the detector specially adapted to detect a particular component
- G01N33/0047—Organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/0285—Nanoscale sensors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
- A61B5/082—Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/497—Physical analysis of biological material of gaseous biological material, e.g. breath
Definitions
- the present invention provides for real time testing of one or more pathogens, diseases, or other conditions of interest in less than five seconds.
- This invention features a device incorporating one or more biosensors to capture and measure volatile organic compounds (VOCs) emitted from the palm of the hand.
- VOCs volatile organic compounds
- This invention is especially useful as a high-throughput access control solution for testing every individual seeking to enter or exit a venue thereby preventing or reducing the spread of infectious diseases wherever large communities traverse or congregate.
- the system and method disclosed is exceptionally fast requiring less than five seconds to assay and report the presence of one or more diseases.
- the system and device does not require the use of any reagents, radiation, or swabs.
- the WAVETM solution requires no specialized training, technological expertise, or operator experience.
- the WAVETM is an intelligent self-contained device providing both auditory and optical cues that permits ' proficient operator training to be accomplished in just a few minutes.
- the system and method is completely non-invasive and requires no touch contact between the device or device operator and the person being tested.
- Operators may include border agents, airline personnel, receptionists, security officers, cruise line personnel, ticket collectors, flight attendants, and the like. To achieve high- throughput access control, all that is required is the ambient atmosphere emitted from the palm of the hand approximately 2-3 inches over the device for approximately 3 seconds.
- Ambient off-gasses include VOCs specific to the individual and the individual's metabolism including the VOC content (signature) specific to a disease of interest.
- VOC content signature
- Each disease or condition has a its own metabolism and thus its own unique metabolic signature, whether the source is viral, fungal, bacterial, prionic, genetic, poisoning, etc.
- Each unique metabolic signature is expressed in VOCs that are recognizable as resulting from the specific disease with a high degree of sensitivity and specificity.
- This invention can detect diseases or conditions that have not yet achieved viral load factors sufficient to be recognized by other assays as well as for individuals who are asymptomatic.
- the biochemical reactions that make up the VOC signature associated with a disease include many different molecules that form a pattern where each disease or condition includes a particular set of reactions associated with a unique VOC pattern/signature for that disease.
- the unique signature is a product of disease related metabolic (biochemical) reactions that differ from normal (healthy) metabolism and also differ from the metabolic events related to other diseases.
- the disease signature can include both the reaction products from the disease genome as well as the host organism's reactions to the invading organism.
- This invention features nanosensing elements that are responsive to molecules (compounds) in close proximity to the sensor surfaces.
- the shape of the compound specifically its electron cloud, determines the intensity and manner of interactions with a proximate nanosensing element.
- Different compounds have different reaction protocols with a given nanosensing element.
- the VOCs do not chemically react with the sensing element surface.
- Each molecule is surrounded by a cloud of electrons, each with a negative charge.
- the clouds surrounding the VOCs interact with the clouds of molecules on the sensing surface.
- VOCs cause the electrons on the sensing surface to respond (Electrons in one cloud repel electrons in the others.), the electronic changes at the sensing surface cascade below to change electronic signaling of the sensor chip.
- the interaction of a VOC compound with the sensor surface decreases the resistivity of the surface effecting an increase in electronic current.
- Using a plurality of different nanosensing elements that interact with different VOCs allows a compound recognition pattern (disease signature) to be characterized from volatile compounds delivered to the sensors as the gas emitted from the subject flows past the sensing elements.
- the recognized signature identifies the source disease at a molecular level thereby achieving exceptionally high levels of sensitivity and selectivity..
- Each nanosensing element comprises a surface that electronically interacts with the electronic features of molecules in its immediate vicinity.
- electroactive serves as an adjective for "electron”.
- the electrons of the proximal molecules disturb the electronic surface of the nanosensing elements.
- the WAVETM is configured to monitor changing current across the nanosensing elements. This change is recorded. The recordings from a multitude of compound nanosensing surface interactions are collated and analyzed, using machine learning and/or artificial intelligence processes.
- a sample of emissions from a small number of persons with an identifiable disease or condition serves to train the the software associated with the device to recognize response patterns specific to that disease.
- the disease profile thus formed is tested with each new subject entry and modified with continuing assay results to arrive at a disease signature that may be incorporated into new or into existing devices with program updates.
- the screening test result is compared to signature library of a specific disease or to a library with signatures for every disease of interest.
- a test result approximating, but not matching any library profile or signature may be highlighted as a potential early indication of a novel health threat, such as a zoonotic disease, industrial accident, or environmental threat. Similarity to a library signature may suggest a novel variant or previously unrecognized strain.
- the device thus can alert to new diseases or increased levels of a known disease (potentially preventing pandemics or epidemics) and/or novel variants.
- the system may initiate profiling the new disease based on a novel aberrant signature before the disease is publicly manifest.
- the nanosensing elements comprise a VOC selective surface disposed atop a gated electronic chip.
- the selective surface interacts with proximal molecules to redistribute the sensor electron distribution and thereby to refocus the electronic properties across the nanosensing surface which alters the electronic properties (signal) of the chip output.
- the chip has a base voltage underlying the sensing surface, a source electrode on the surface, a semi-conductor between the source and a drain electrode, and analytical hardware to detect, process and analyze electronic change events.
- the potential or the electromotive force between the source and drain electrodes is preferably between ⁇ 0.1 and 5V, more preferably designed in a rage about 1 - 3V.
- the chip current (flow from source to drain) is under control of the interaction between the nanosensing surface and nearby electronic influences.
- a VOC shifts the interaction with the semiconductor bridge between the source and drain to increase conductance the increased current is detected and analyzed.
- the changes in current flow sensed by each nanosensing element are monitored, collated and processed to identify disease specific patterns associated with these VOC interactions.
- the device preferably features one or more arrays of chips with each array outfitted with nanosensing elements designed to have different sensitivities, different affinities for different VOCs.
- the sensitivity determinants on the nanosensing elements are molecules added as “decorations” or functionalyzing agents on the nanosensing element surface. These decorations will differentially attract (electronically react with) proximate VOCs. The time that a VOC lingers in close approximation with the nanosensing surface is one factor for recognizing a type of interaction. The magnitude of change is another. Time to peak value, slope of signal change (up and/or down), peak shape, over several differentially decorated sensing elements are available factors for defining the disease signature. Peak values or values averaged over time of the interaction (with a signal sensed in excess of a predetermined threshold value) are preferred factors for Al analysis in defining the disease signature patterns.
- a high discrimination mode as the VOCs approach the nanosensing surface, a continuous recording of the interactions is analyzed.
- the VOC molecular configuration and/or orientation will change as it interacts with and is influenced by the nanosensing surface. This twisting or bending of the VOC can be a feature the device uses to recognize a specific VOC of interest.
- the high discrimination mode is not an essential feature of the device's functions. In preferred embodiments where a sensing array is configured with a plurality of differently functionalized nanosensing elements, not every sensing element will interact with every occurrence of a specific VOC in a sample. Multiple copies of each type of nanosensing element increases the probability of interactions between at least one nanosensor surface and the potentially relevant VOCs.
- the high discrimination mode is not a necessity for high- throughput screening practices.
- the redundancy increases the sensitivity and selectivity of the device as many VOCs will bypass one or more nanosensing elements.
- the pseudorandom flow and geometry of the device mean that not every VOC will become proximate to every nanosensing element. Redundancy (multiple copies of similarly configured elements) allows averaging to reduce the random differences between samples.
- the interaction between the proximate VOCS and nanosensing surface is transmitted through the sensing element to modulate current flow.
- the bias voltage and/or potential are set in the device and may be identical across all sensing elements, a subpopulation of sensing elements, such as a chip, a row, column, quadrant, or block on a chip, or individual elements on a chip. In high-throughput screening operations, referred embodiments simply use the same bias ans potential for all sensing elements.
- the electronic sensing elements are controlled by a controller, preferably a digital to analogue converter that converts computer or algorithmic instructions to produce analogue voltages (potential) for the sensors.
- a controller preferably a digital to analogue converter that converts computer or algorithmic instructions to produce analogue voltages (potential) for the sensors.
- An analogue to digital converter accepts the analogue signals and converter them to digital data that a computer analyzes, sorts, and stores. Hardware to collate and stream the data may be involved in the processing data for computer analysis.
- the computer may be on board, physically attached through an interface, or interfaced with a remote device.
- the device When used in its preferred mode, that is, reading the off-gasses emitted from the underside or palm of a hand, the device is set for use in a real-time analysis seting, i.e., high-throughput screening for facility access. Gases are delivered from the person moving their hand over the device allowing the emited ambient gases to interact with the nanosensing element surfaces of the device. A negative pressure, device v. ambient, draws gases ambient to the sensor device through a port and across at least one sensing array of chips. As gases flow across and interact with the sensing surfaces electronic output data are obtained. These interactive data are collated and analyzed. The result is compared with one or more signatures associated with a disease or diseases.
- a real-time analysis seting i.e., high-throughput screening for facility access.
- Gases are delivered from the person moving their hand over the device allowing the emited ambient gases to interact with the nanosensing element surfaces of the device.
- a negative pressure, device v. ambient draws
- a match indicates that the device was exposed to emited gases associated with that disease or condition.
- the person whose VOCs matched a disease signature of interest is flagged for, e.g., denial of entry to a zone, direction to a positive match zone or location, additional screening, etc.
- the device operates simply by receiving a gas sample from a subject source for analysis.
- the gas sample is preferable an easy to obtain personal offgas, such as from the palm of the hand.
- An exhaust fan configured in the device can provide a negative pressure that draws or intakes the ambient gases through an intake port into the device to flow over the nanosensing elements. When a hand passes within few inches of the device entry port, vapors from the hand are included in these ambient gases.
- An intake process may be activated by a timer, a heat activated switch, a motion activated switch, a light (or diminished light) activated switch, a voice or noise, an operator, etc.
- the device preferably includes an on/off switch that may be manually operated.
- a timer may increase flow for a specified collection time.
- a heat or motion activated switch may activate the device when a subject approaches or a hand is presented.
- An operator may control the operation manually, by voice, user interface, or other commands.
- the electronic interactions sensed by the sensing elements are recorded and converted to a digital signal that is compiled and streamed to a data processor.
- the data are processed to produce a resulting pattern (profile) that can be compared to signature(s) for a disease of interest, to a select number of signatures associated with one or more disease of interest, or to a library of all disease associated signatures.
- a disease of interest may be associated with a plurality of signatures.
- an infectious phase and a resolution phase of a disease may be associated with different signatures.
- Different signatures indicative of a disease may be produced by persons presenting with one or more cofactors, for example, male or female, pregnancy, alcohol intoxication, fasting state, etc. The cofactor does not need to be identified prior to testing. Simply, the machine learning algorithms may have associated different signatures with the same disease under different cofactor conditions.
- a library of VOC profiles and signatures associated with one or more selected diseases or conditions is produced for comparison with the subject's data that is produced by the device with each sample reading.
- the profiles and signatures held in the library of interest are developed using a machine learning or teaching process involving a selected group of subjects known to have symptoms associated with the disease or condition of interest and to have a confirmed diagnosis for the disease.
- Members of this group produce thousands of VOCs, many of which result from healthful biochemical reactions, but a fraction of which are particular by their presence, absence, concentration, or ratio with another compound or compounds, in a combination unique to the identified disease.
- the combination defines the signature for the associated disease.
- each definitive result may be used to strengthen or refine the library match process.
- a group of subjects not identified with a particular disease may have their VOC results used as a negative disease control, i.e., indicative of VOC patterns that are not disease associated.
- the various disease groups can strengthen reliability by serving as negative controls for other diseases. Such "negative control" readings can serve as confirmation that an acceptable screening read has been completed.
- Subjects with a disease or condition other than that for which a signature is under development can serve as negative comparative controls for that signature.
- a subject may be diagnosed with a condition such as prostate cancer, strep throat, cystic fibrosis, chronic fatigue syndrome, measles, Alzheimer's disease, gout, flu, bone fracture, hepatitis (A, B, C, D, E), lead poisoning, etc., but not Disease A.
- a condition such as prostate cancer, strep throat, cystic fibrosis, chronic fatigue syndrome, measles, Alzheimer's disease, gout, flu, bone fracture, hepatitis (A, B, C, D, E), lead poisoning, etc., but not Disease A.
- a preferred application of this invention is its use as a screening device for controlling access to a venue.
- a person is instructed with signs, video, and/or auditory instruction to place a hand over a port or screen on the device.
- the person is instructed to move the hand away.
- a video or a set of cartoons will guide the subject to position the palm of the hand about 2-5 inches from the device sampling port. This movement of the hand may be adequate to deliver a sample from the person to the nanosensors and to produce the sample data for comparison to profiles or signatures in the library.
- the palm off-gases are drawn through a port on the device surface to flow over the sensors.
- a sampling time ⁇ 2-5sec preferably ⁇ 3sec, delivers the subject's VOCs to the device for analysis.
- Current computation time is about 3sec.
- a purge to clear that subject's VOCs from the sensor zone commences during the data processing and may continue until the next subject exposure. The subsequent exposure may be triggered, for example, by a temperature or motion sensor associated with the device.
- a purge time of 5sec supports a read rate of 7.5 subjects/min.
- the sensing elements report normal VOCs (those associated with the human species and not a particular disease or condition).
- An "AllClear"TM verbal or visual indication allows the subject to enter the venue. But when profiled VOCs are present the device can alert the subject stand aside or provide instructions to an attendant at the machine or along the venue entry pathway to deny entry or to instruct the person that additional screening may be required. The additional screening may be on site or may require a delay (denial) for entry at that occasion.
- the level of normal VOCs detected serves as an indicator that sufficient subject VOCs have been presented to the device.
- the device signals an AllClearTM when a threshold amount of VOCs have been read and no matching disease profile or signature has been observed.
- a timer may be set to terminate a sampling session when the threshold amount of VOCs has not been observed in a reasonable time.
- the exhaust/intake fan continues to pull ambient gas through the device to purge between subject samples.
- the purge flow may be set to a higher flow rate than that used in sample reading.
- a completed test result that does not match a signature of a disease of interest is granted access.
- Such grant may be indicated by the AllClearTM, a light, sound, or action such as a gate movement, indicative that the person does not express the disease of concern and can continue through the access portal.
- the clearance e.g., an "AllClearTM" notice, may be communicated in words or other recognizable output signal, for example, a green light, a progression of lights along a strip; a positive tone, chime, or RIF; a verbal confirmation or instruction; a gate opening; a gate not closing; a moving walkway; or seat activation; etc.
- the signal indicating lack of positive match signal may similarly be delivered by any acceptable means, e.g., light, barricade, sound, etc.
- the subject profile matches that of a disease of interest, the subject would be instructed to undergo additional assessment, perhaps taking off a glove or rubbing hands to stimulate circulation.
- a non-passing determination instruction or action may guide the person to secondary assessment or to seek further testing, deny entry entirely, restrict admittance to an alternate section, etc.
- Secondary assessments may be provided in a number of formats. For example, they may require the subject to simply repeat the test a second time or to step into a separate line for a longer time analysis. The subject may be instructed to remove his or her gloves and present the hand for retest. Secondary assessments might also involve testing gases from another body part.
- a wand or hand held sniffer connected by an umbilical cord to the device or an alternate device may be used to draw a sample from ambient gas around a portion of the subject, e.g., the neck, armpit, forearm, leg, etc., and then to deliver the gas to the original device or to a dedicated secondary assessment device.
- the wand may briefly store a sample for delivery to the device.
- a wand may itself include nanosensors similar to those in the primary device, but rather than in a box shape, have nanosensing elements disposed in a rod or tube to collect samples from another body area, e.g., the back of the neck, the mouth expelling breath, an armpit, etc.
- the device may use the wand as an adjunct sensing tool to be used for screening persons not able to deliver their samples to the sensing module.
- a person may not have free use of a hand to present to the testing surface; assessing an amputee may require access to a body part other than a hand.
- An injury may make it impossible, painful, or inconvenient for a subject to present their hand to the device for screening.
- a toddler or infant may be in a backpack, stroller, carriage, etc., and thus unable to place its hand properly for screening.
- the wand acts as a tool allowing a device operator or a subject's colleague or guardian to direct the air collecting port in the wand at an alternate body part (or from a hand of a person who is unable to present it themself).
- the tip of the wand is directed near the alternate source of the emitted gases.
- the wand may be in a continuous draw mode as it is guided towards the subject, it may start drawing in gases when moved, it may include a trigger or button to activate gas collection and delivery.
- the drawn gases continue through the wand to access the sensing chip(s) where the screening is effected, e.g., in the wand device or near or at an exit from the wand device.
- the wand may be used as an adjunct test on non-humans, i.e., to assess object rather than persons.
- a disease carried on a parcel, bag, etc., carried by a person would serve as a subject for , e.g., farm borne diseases.
- An agent would merely point the wand to the area of targeted handbag, etc.
- This preferred box shape embodiment would be available for use in a wide variety of placements. It may be set up at any angle, e.g., vertically, horizontally or any angle in between.
- the nanosensing elements of the device may be configured as a flat surface, flat surface surrounding a recessed area designated for receiving a hand, a curve, a ring, a closed or open shape to accept a hand or other body part - any shape that allows the test subject to deliver emitted off-gasses to the device sensing zones.
- the device may be designed and delivered for use in many applications including, but not limited to: a countertop, a turnstile, a wall or barrier defining a walkway, an arched entrance or exit, an escalator, an enclosure (cubical, booth, security scanner, dressing room, outfiting room, phone booth, elevator, etc.), a tent for a meeting or show, a nightclub, a cabaret, a house of worship , a bar, a club, a bank, a cruise ship, a fraternity, a sorority, a funeral parlor, a birthing center, a train, an airplane, a frigate, a cruise ship, counter, a tourist attraction, a theme park, an aircraft carrier, a factory, a subway platform, a public conveyance, a tunnel, a dining room or cafeteria, a restaurant, a hallway, a zone, a secured area, a classroom, a hospital, a courthouse, a coliseum, a stadium, a
- a concert venue may use the device in an embodiment that includes a ticket scanner, whereby a person seeking entry would require the ticket in addition to the VOC AllClearTM result for admittance.
- venues may wish to incorporate a physical ID reader, e.g., an RFID, a scanner, a bar code, QR code, palm print, fingerprint, facial recognition, or other personal identification to be checked against databases to confirm that the person has a need to enter, at the same time a person receives an AllClearTM designation.
- a primary application of this invention is for protection and safety of the traveling public which a fundamental component of commerce, both local and international. As such, municipalities, municipal authorities, etc.
- WAVETM technology associated with the present device for use at airports, train stations, bus terminals, ferries, etc.
- local authorities will use this technology to expedite customer access and movement by combining multiple steps in the security, check-in, validation, etc., in combination with the health screening protocols.
- PNR Passenger Name Record
- the departing passenger When interfaced with the passenger database, the departing passenger could be informed of the terminal or gate of the flight, flight delays - if any, weather at the destination, boarding status, etc.
- the passengers undergoing health screening may be informed of baggage information, connecting flights, messages relating to hotel, rental car, etc.
- a biometric ID check incorporated with the device may eliminate the need for paper documents, such as ID cards, tickets, boarding passes, baggage checks, etc.
- the VOC scan incorporated with personal identification may instruct the subject to a floor or room number and elevator to access the room and ask for a response whether help with baggage or any special treatment is needed.
- a separate punch clock would no longer be necessary.
- entry and exit times may be recorded to validate that persons are served in order.
- a time flag may be built in when a subject fails to exit when expected to either search for that individual or remove them from the queue.
- the device at the time of access screening can inform other participants of the additional arrival or last person to arrive.
- the palm print or a portion thereof may be a preferred biometric in an associated reading device.
- the biometric ID check may interface with other databases, e.g., the Do Not Fly List, or other list and alert authorities for possible additional attention.
- the screening device with its optional adjuncts operates continuously with minimal operator input required. When incorporated with a gating system, the system controls access automatically. Personnel requirements associated with using the device are low allowing more efficient assignment for employees. Problems with employee alertness due to shift changes are minimized or avoided.
- the venue access screening primarily concerned with a communicable disease is a primary function of the device, use in combination with accessory sensors and database access improves access control and customer service while incorporating other tasks involving data obtained during a single scan or reading.
- the device While assessment of metabolic diseases is a primary function of the device, the device may be programmed to operate in a mode where VOCs carried on an individual, an individual's clothing, a package, etc., may be monitored. This program mode looks at content of, or recent exposure to, possibly dangerous or hazardous molecules. These may include but are not limited to: explosives, explosive ingredients, explosive residue, toxins, environmental markers, etc. In the non-metabolic VOC operations, persons may for example, be screened or cleared to exit an area zone that might have been associated with a release of a toxic substance.
- the device While the device is designed for controlling admittance of individuals passing through a checkpoint, the device may be put to use for detecting presence of a condition or disease in a less controlled crowd situation. In a location where a crowd gathers or passes through, the device might not be targeted to screen individual subjects to prevent their entry, but perhaps to count the number of passersby presenting with a disease of interest or to a selected group of diseases.
- This application is particularly useful for public health officials when monitoring the introduction, spread or waning of one or more of the diseases including locations where disease spread is happening or is more likely.
- a public transport system such as a subway where persons entering and exiting specific stations can be assessed, even anonymously.
- the primary sourcing stations and disease stations can be used for mitigating disease spread. Track and Trace is expedited by identifying major sources and locations of likely contact of the infected individuals with others at the locations of disease exit.
- the device is or is part of a system that comprises: a control component, a sensing component, a data delivery component, an analytical component, an information storage component, and a reporting component.
- the primary sensors are nanosensing elements that monitor VOCs in real time.
- Other sensors in or associated with the device may include operational features including, but not limited to: an on/off switch, a WiFi or Bluetooth detector, a motion detector, a temperature sensor, a proximity sensor, a time sensor, a global positioning sensor, a light detector, a sound detector, etc.
- the primary sensors react to the electrical properties of a molecule in close proximity. Weak influences, attractive or repulsive result in a change in the electronic characteristics on the sensor surface. Different VOCs will influence and be influenced by the nanosensing surfaces. These changes or interactions will be repeatable for the same molecules closely approximating the sensor surface.
- the decorations or functionalizing compounds interact with the VOCs.
- Aromatic, cyclic hydrocarbons and heterocyclic compounds frequently interact with a large variety of VOCs.
- Nucleic acids such as DNA strands are preferred functionalyzing compounds.
- the heterocyclic rings in the nucleic acids assist in securing the nucleic acid to conductive surface on an electronic chip.
- Nucleic acids are also a preferred decoration because of their variability and ease of production. Different sequences of the four natural nucleotides, for example in a sequence with just eight nucleotides, provide over 4,000 available sequence structures to choose from. Longer strands provide better adhesion and more sequence structures to choose from. Using synthetic nucleotides in addition to the four, further increases the number of choices available.
- a preferred semiconductive surface on an electronic chip comprises elemental carbon.
- Single layer planes or tubes of carbon are especially advantageous for their retention of decorations such as biologic molecules, which contain a lot of carbon atoms, but also for compactness and capacity to transmit electronic fluctuations occurring as decorations are affected by proximal electronic (VOC) influences.
- Single layer two dimensional graphene may also be used in some embodiments by themselves or in conjunction with Single Wall carbon NanoTubes (SWNTs). Crumpling the graphene so that it does not lay flat can increase surface area and allow for 3-dimensional fiting of decoration molecules.
- SWNTs with their tubular carbon structure are a preferred carbon base for transmiting the current and adhering to the decorations.
- the carbon base preferably formed with semiconducting SWNTs, is adhered to a dielectric chip surface, such as Hf0 2 .
- a preferred density is about 50 nanotubes/linear micron (of ⁇ 3m) across a preferred nominal chip width of ⁇ 3-10m.
- Functionalized area 250 x 500 microns The nanotubes can be applied by bathing the nascent chips in SWNTs in toluene. But this method involves cumbersome masking etching and cleaning.
- SWNTs are delivered by the vendor in toluene. With each dip or bath, the concentration of nanotubes decreases. The nanotube coating from the first bath is different from the later batches.
- Array 4x4 16 transistors 250x500. CNT covers all 16.
- the preferred method of coating the chip surface avoids the nanotube density variability from first to last bath and does not require the masking, etching and cleaning steps. Nanotubes are precision applied to each sensing element. The chamber is fed toluene
- IB as a vapor or from a heated compartment containing toluene.
- the feed rate of toluene polymer wrapped 1.2-1.4 2 micron diluted with an inert gas or heat applied to the toluene compartment controls the toluene vapor pressure.
- the carbon nanotubes are misted through an atomizing nozzle to apply the carbon directly on the Hf0 2 surface between the source and drain electrodes.
- the toluene atmosphere is controlled at about to slow drying thereby allowing the nanotubes freedom to orient evenly on the surface thereby eliminating, reducing, or minimizing the coffee ring effect commonly observed with droplet drying.
- the functionalyzing agents are then micro pipetted onto the carbon nanotube surfaces with controlled humidity, ⁇ 90%, to promote even drying and to avoid the coffee ring effect.
- the Hf0 2 dielectric base underlying the current carrying carbon layer is preferably about 20-90nm thick.
- the Hf0 2 is preferably evenly spread using a process such as atomic layer deposition.
- a Hf0 2 coating preferably about 30-50nm. More preferably ⁇ 40-45nm, sits atop an Al 2 0 3 base on a standard chip, such as silicon dioxide.
- Al 2 0 3 base supporting the Hf0 2 is preferably about 3-20nm, preferably deposited using chemical deposition of aluminum that is allowed to oxidize or atomic layer deposition.
- the nanosensing elements can be of a variety of preselected sizes (areas, dimensions, diameters), heights (due to stacking density), shapes and configurations.
- a nanosensing element SWNT surface is decorated with a single species of biomolecule, often a nucleic acid such as RNA or DNA with a length between 8 and 25 nucleotides.
- the SWNT interface surface on the chip ' generally accept cyclic, especially polycyclic compounds, e.g., porphyrins, phthalocyanines, and azobenzene, as non-covalent associations on their surfaces.
- Polymers such as the nucleic acids, polyethylene glycol, and fatty acids - especially those conjugated with short polypeptides also form stable surface interactions with the single layered carbon structures and thus are available choices as functional groups on the nanosensing element surfaces.
- Modified nucleic acids with e.g., nucleotides other than the standard A, C, G, and T and/or incorporation of other molecules in the complex, e.g., stable nucleic acid lipid particles (SNALPS), offer additional choices for detection variations.
- SNALPS stable nucleic acid lipid particles
- the assembly of SWNTs decorated with such addons is well-known in the art. Therefore one skilled in the art does not require a repeated teaching in this paper.
- Preferred embodiments include chips and arrays that have several different functionalyzing decorations.
- the device may be configured as a circuit card or a collection of circuit cards. Each card supports a plurality of sensing elements both physically and interconnectively.
- a digital to analogue converter powers the nanosensing operations. Digital instructions are converted to dictate or influence analogue values, for example of temperature, bias voltage, gate voltage, etc., on the nanosensing elements.
- An analogue to digital converter accepts input from the nanosensing elements and produces digitized data. The data are organized and streamed by a controller of the outputted signals. Inputs from a plurality of simultaneous measurements, e.g., current fluctuations, are organized and combined in a stream of data for computer analysis. Interfaces that connect the different functions and components are provided.
- a plurality of computers may be interfaced to work in or with the system.
- a NUC computer may process the sensor results in an on board operation.
- the on board computer may interface hard wired or remotely with one or more adjunct computers, e.g., at a testing station or remotely in a central collection and processing facility (e.g., for data security) or across outside computational support such as a "cloud" service vendor.
- Power can be through a battery or remote delivery, that is provided by a source outside the main device cabinet. Power delivered through an external source is preferably delivered through a device battery to remove electrical noise. The outside power will often be delivered electrically through conductive cabling, but other means of power transmission, e.g., inductive pickup, light beam, solar panel, etc., can work as well.
- a gate voltage serves as differential that allows current to flow. The current flows, in response to alterations in a bias voltage that changes in response to electronic interactions between the VOC and the nanosensor and the nanosensor support. These voltages maybe under directions delivered through the digital to analogue converter.
- a bias voltage may be selected as optimized depending on the nanosensing elements and supports chosen.
- a lOOmV to 2V bias is compatible with many devices. But the allowable range may span several orders of magnitude. For example bias voltages in the order of lOmV, lmV, 100pV, 10pV, lpV, or even in the nV range may find some applications. Similarly, bias voltages greater than lOOmV, e.g., in the order of IV, 10V, 100V, 1,000V may be useful in other applications.
- a gate voltage ⁇ 1-5V modulates the source-drain current. A value of ⁇ 3V is easy to achieve and corresponds to two regular alkaline batteries.
- the gate voltage may be reduced.
- the current flow is a design choice meaning that the direction of flow (changing voltage from plus to minus) depends on configuration choices.
- An exemplary nanosensing cartridge array may comprise an array of 256 nanosensing elements arranged in a 4 x 4, 8 x 8, or 16 x 16 grid. While each element or a selection fraction of elements, e.g., a 4 x 4, or 8 x 8 block, a column or a row, may be individually manufactured to have its unique decoration, the ease of manufacture and advantages of redundancy suggest building chips of: e.g., 256, 400, 512, 1024, etc. Individual sensing elements or groups of sensing elements may present with different temperature or bias voltages though on the singly decorated chip so not all elements will interact identically.
- sensing blocks Redundant sensing elements, sensing elements made to the same specifications are referred to as "sensing blocks.” Use of blocks with a plurality of members can reduce response variability and allow continued operation when a nanosensing element malfunctions.
- a basic 4 x 4 sensing block renders 16 sensing blocks in a 256 chip array cartridge.
- a preferred arrangement has 16 different selective decorations, 1 for each sensing block.
- a device with 2 such cartridges presents with capacity for 32 different sensitivity modifications in 4 x 4 sensing blocks, with each such block accordingly having 16 copies with the same interactive surface molecule.
- a circuit card holding a chip cartridge with multiple, e.g., 16 sensing blocks can serve as an electronic component central to the sensing operations.
- 256 element chips may be arranged in a 4 x 4, 4 x 8, 4 x 16, 2 x 4, 2 x 8, 2 x 16, or other selected geometry of 16, 8, 4, 32, 16, 32, sensing blocks, respectively.
- chips may be disposed on opposite sides (front and back, top and bottom) of a circuit card.
- the number of elements on a chip is a design choice. This example using 256 was chosen for its analogy to computer circuitry where powers of 2 are common. Continuing with this theme designers may prefer chips with 128, 512, 1024, 2048, 4096, etc., sensing elements.
- Incorporating sensing elements on both sides of a chip is an obvious method for doubling.
- chips are arranged in a square, a factor of 4 would be observed.
- the designer is not bound to follow these conventions, a chip with any convenient number of sensors is possible, e.g., 25, 81, 625, etc., 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 51, 54, 57, 60, etc., 36, 49, 64, 100, etc.
- the sensor blocks on such chips need not be the same size. (the same number of elements.
- a 256 element chip array might be configured as a 16 x 16 grid pattern (0-15 for column numbers and A-P for row numbers).
- 0-3:A-D might be a first sensor block of 16 elements decorated with nucleic acid nai.
- a second sensor block also of 16 elements at 4-ll:A-B might be decorated with nucleic acid na 2 ;
- a third sensor block of 32 elements at 12-15:A-H might be decorated with nucleic acid na 3 ;
- a fourth sensor block of 8 elements at 0-3:E-F might be decorated with nucleic acid na 4 ;
- a fifth sensor block of 32 elements at 0-7:M-P might be decorated with nucleic acid na 5 ;
- a sixth sensor block of 12 elements at 4-7:C-F might be decorated with nucleic acid na 6 ;
- a seventh sensor block of 40 elements at 7-ll:C-J might be decorated with nucleic acid na 7 ;
- an eighth sensor block of 32 elements at 0-15:K-L might be decorated with nucleic acid na 8 ;
- a designer may choose any convenient arrangement and number of chips on a card or in a device. For example, square arrangements of chips, 3 x 3, 4 x 4, 5 x 5, 6 x 6, 7 x 7, 8 x 8, 9 x 9, 12 x 12, 16 x 16, 32 x 32, etc., may be convenient. Columns of chips, e.g., 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 32, 64, etc., may be chosen for a rectangular arrangement. For such rectangular arrangements, the rows likewise can be of a number convenient to the designer.
- 4 cards may serve as box walls, with opposing sides of the box having sensor components facing one another. Since 1, 2, 3, or 4 sensor cards are sufficient with additional cards adding to redundancy, this style of disposition allows for the card or cards with the greatest signal (perhaps closest to the hand or closer to the tissue with best off-gassing) to signal data collection endpoints when a threshold of VOCs has been detected.
- different cards may be optimized to detect different diseases or to operate at different temperatures.
- the activated card may be auto- selected, e.g., for ambient temperature, or remotely or locally selected for the disease of interest.
- Pentagons, rectangles, hexagons, triangles, curved shapes, regular or irregular are suitable designs for housing the sensing components. Additional redundancy improves durability (time between maintenance) and has a valuable feature of allowing cross checking during calibration cycles. The number of sensors and separate sensor chips is therefore a design choice. If a single chip or even a single card appears faulty, the redundancy allows the device to continue operations. Redundancy is a design choice to be decided by the designer, manufacturer, purchaser, regulative body, etc.
- the sensing circuit cards are not confined to box shaped disposition.
- the sensing plate or card may be situated on or recessed in a surface vertically or horizontally, e.g., in a countertop or railing as an example for assessing persons on a walkway or moving walkway.
- a zone adjacent to a doorbell or an elevator button may be outfitted with a sensing module.
- the device may be portable, i.e., available for a person to carry in a case.
- the device may be fixed in a building structure or as part of an entryway to a building or part thereof.
- a portable device may include attachments allowing vertical, horizontal or other angle disposition. Any flat or curved surface may be configured as a device retainer and therefore a screening location.
- some may be arranged in a parallel orientation for simultaneous subject exposure, others may be arranged in series such that opportunity for exposure of the subject gases to the sensor components is along a time sequence.
- the device is preferably programmable in one or more respects.
- a simple programming operation involves activating or turning on the device.
- the device is also controllable through the electronics and permitted access of gases to the sensors e.g., though a slide port.
- the sensors or data collection, analytical and/or storage functions may be under program control, for example, by operator interface, subject interface, motion, detection, time interval, a screening sensor that activates other sensing components or functions, a remote control, etc.
- the program may be selected from a collection of programs stored for the machine to select from. Programs may be delivered from a centralized location such as a company, home office, a local office, a security, room, an inserted instructional or datacard, etc.
- the interface carrying the program may feature a component including, but not limited to: a keyboard, a touchscreen, a chip (such as a USB chip) a microwave transmitter and receiver, a WiFi connection, Bluetooth, an e-pen, a port for plugging in a chip, a phone, connection, a computer, a computer memory and program storage device, an app on a connected or remote electronic device, a dedicated tap and touch pad or screen, a microphone with voice deciphering capability, biometric security modules (e.g., face recognition, voice recognition, fingerprint, keyboard patterns, etc.). Additional security may include features including, but not limited to: access coding from a person or machine, encryption, confirmation required by a system manager, etc.
- a component including, but not limited to: access coding from a person or machine, encryption, confirmation required by a system manager, etc.
- the programming may be as simple as activating the device or a portion thereof.
- the programming may select one or more diseases for matching.
- the programming may incorporate additional learning cycles.
- the programming may interactively adjust one or more sensor's parameters such as adjusting temperature, a voltage, a weighting applied to a sensor's or a group of sensor's outputs, a screen that may divert gas or direct the gas more strongly at a particular sensor or group of sensors.
- the device is adaptable and programmable for application in different environments or applications. Outdoors or in environments with flow, a windscreen may be affixed on the device to facilitate capture of subject emitted gases by shielding the zone surrounding the sensing area from convection currents that may convey the VOCs past or away from the sensing elements. Lighting may help direct the subject to the test device and/or direct the subject how and where to place or move the hand. Light intensity may be increased for dimly lit access areas or for outdoor use at night.
- Disease libraries with their profiles and/or signatures can be added or deleted as concern for a disease grows or wanes.
- Program updates may be frequent for some diseases as variants change prevalence.
- Emerging diseases, such as COVID-19 in the early 2020s, can be incorporated in the programming as the disease becomes recognized.
- Different venues may feature different programming. For example, a positive test at some venues may simply advise the subject and deny entry. In a different venue, an escort may be summoned to guide the subject for further assessment or treatment.
- the programming in a particular device may direct comparison to a single disease or condition of interest, to a select group of diseases, to diseases with associated signatures, to a set of toxins, or other comparisons selected by the user.
- Program updates to add or adjust profiles or signatures can keep the device current.
- Programming may be effected using any acceptable interface or interface method. Programming may require a hardwired or plug in device when strict control is observed. Wireless updates may be accomplished automatically or on request. While the methods related to using the device to recognize signature patterns of diseases do not require identification of the molecular structure of the VOCs or other compounds detected, knowledge of specific molecules that are involved in a disease signature can act as a factor in improving the device.
- Identifying the compounds instrumental in forming the disease signatures can be applied to, e.g., selecting a decoration or decorations for the sensing elements, adding scavenger compounds to differentiate between similar compounds, adjusting a voltage or temperature, adding a pre-read filter, etc.
- time for evaluating each subject sample, sensitivity and/or selectivity of the device may be refined by chemical analysis, including, but not limited to: x-ray fluorescence spectrometry, ion chromatography, gas chromatography, gas chromatography- mass spectrometry, inductively coupled plasma mass spectrometry, inductively coupled plasma optical emission spectroscopy, scanning electron microscopy, x-ray diffraction, electron probe microanalysis, nuclear magnetic resonance, etc.
- the device may be programmed to screen objects passing by on a belt .
- the device itself be motile to pass by or over objects of interest.
- the wand/umbilical tube embodiment may be used in this manner for example as a tabletop mount, a portal mount, a belt mount, a chest or backpack mount.
- Controls may be incorporated into the wand itself or in the sensing module of the device.
- the operator may target the exterior in general, one or more parts of an item, e.g., a seam, an opening, a taped area, etc.
- An open or broken container may be tested to determine degree of hazard to handlers or the public.
- the programming may be installed in a device to allow switching between detection targets.
- the device may be configured for a select group of detection targets. Programming for modes not originally installed in the device or accessible to the device may be added using a contact, e.g., plug-in connection, or may be delivered through remote transmission.
- the device may be part of a system of devices where the experiences of each device are delivered into a cloud or other inclusive data set.
- the system continues to analyze the data and notifies device operators when updates are available or when instructed by the operator or in concert with regulations delivers downloads to the relevant devices. Additional assessments may involve a screen that does not involve VOCs as tested by the device, including, but not limited to: a biosample (e.g., PCR or antigen), a thermal reading, an x-ray, etc.
- a biosample e.g., PCR or antigen
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Abstract
This invention provides a system and method for the manufacture, functionalization and related methods of a device for real time testing of a pathogen, a disease, or other condition of interest. This invention is especially useful fortesting every individual entering or exiting a venue or transitioning through any controlled entry or exit zone demarcated by a portal, passage, security zone, or gate, etc. The testing requires no invasive sampling or even touch contact - between the device or device operator and the person being tested. The ambient atmosphere surrounding the individual contains volatilized off-gases (VOCs) from that individual. These off-gasses include volatile organic compounds specific to the individual and the individual's metabolism.
Description
High-Throughput Real Time Bio-Threat Screening
The present invention provides for real time testing of one or more pathogens, diseases, or other conditions of interest in less than five seconds. This invention features a device incorporating one or more biosensors to capture and measure volatile organic compounds (VOCs) emitted from the palm of the hand. This invention is especially useful as a high-throughput access control solution for testing every individual seeking to enter or exit a venue thereby preventing or reducing the spread of infectious diseases wherever large communities traverse or congregate. The system and method disclosed is exceptionally fast requiring less than five seconds to assay and report the presence of one or more diseases. The system and device does not require the use of any reagents, radiation, or swabs.
The WAVE™ solution requires no specialized training, technological expertise, or operator experience. The WAVE™ is an intelligent self-contained device providing both auditory and optical cues that permits 'proficient operator training to be accomplished in just a few minutes. The system and method is completely non-invasive and requires no touch contact between the device or device operator and the person being tested.
Operators may include border agents, airline personnel, receptionists, security officers, cruise line personnel, ticket collectors, flight attendants, and the like. To achieve high- throughput access control, all that is required is the ambient atmosphere emitted from the palm of the hand approximately 2-3 inches over the device for approximately 3 seconds.
Ambient off-gasses include VOCs specific to the individual and the individual's metabolism including the VOC content (signature) specific to a disease of interest. Each disease or condition has a its own metabolism and thus its own unique metabolic signature, whether the source is viral, fungal, bacterial, prionic, genetic, poisoning, etc. Each unique metabolic signature is expressed in VOCs that are recognizable as resulting from the specific disease with a high degree of sensitivity and specificity. This invention can detect diseases or conditions that have not yet achieved viral load factors sufficient to be recognized by other assays as well as for individuals who are asymptomatic.
The biochemical reactions that make up the VOC signature associated with a disease include many different molecules that form a pattern where each disease or condition includes a particular set of reactions associated with a unique VOC pattern/signature for that disease. The unique signature is a product of disease related metabolic (biochemical)
reactions that differ from normal (healthy) metabolism and also differ from the metabolic events related to other diseases. The disease signature can include both the reaction products from the disease genome as well as the host organism's reactions to the invading organism.
This invention features nanosensing elements that are responsive to molecules (compounds) in close proximity to the sensor surfaces. At a molecular or atomic scale, the shape of the compound, specifically its electron cloud, determines the intensity and manner of interactions with a proximate nanosensing element. Different compounds have different reaction protocols with a given nanosensing element. The VOCs do not chemically react with the sensing element surface. Each molecule is surrounded by a cloud of electrons, each with a negative charge. The clouds surrounding the VOCs interact with the clouds of molecules on the sensing surface. As the VOCs cause the electrons on the sensing surface to respond (Electrons in one cloud repel electrons in the others.), the electronic changes at the sensing surface cascade below to change electronic signaling of the sensor chip. The interaction of a VOC compound with the sensor surface decreases the resistivity of the surface effecting an increase in electronic current. Using a plurality of different nanosensing elements that interact with different VOCs allows a compound recognition pattern (disease signature) to be characterized from volatile compounds delivered to the sensors as the gas emitted from the subject flows past the sensing elements. The recognized signature identifies the source disease at a molecular level thereby achieving exceptionally high levels of sensitivity and selectivity..
Each nanosensing element comprises a surface that electronically interacts with the electronic features of molecules in its immediate vicinity. In this context "electronic" serves as an adjective for "electron". The electrons of the proximal molecules disturb the electronic surface of the nanosensing elements. When the electrons of the sensing surface shift in response to the electronic interactions with the passing molecules, the current or other electronic activity of the chip is altered. The WAVE™ is configured to monitor changing current across the nanosensing elements. This change is recorded. The recordings from a multitude of compound nanosensing surface interactions are collated and analyzed, using machine learning and/or artificial intelligence processes. In this practice, a sample of emissions from a small number of persons with an identifiable disease or condition (often shortened to "disease" in this discussion for simplification) serves to train the the software
associated with the device to recognize response patterns specific to that disease. The disease profile thus formed is tested with each new subject entry and modified with continuing assay results to arrive at a disease signature that may be incorporated into new or into existing devices with program updates.
A large number of interactions will be with ambient gases and common human metabolites. A relatively small fraction of interactions will be relevant to any one screening or detection task. The machine learning processes will help the device ignore the irrelevant or non-contributing interactions and to concentrate on optimizing data collection and processing those interactions illustrative of a condition of interest. In a comprehensive assessment mode, the screening test result is compared to signature library of a specific disease or to a library with signatures for every disease of interest. A test result approximating, but not matching any library profile or signature may be highlighted as a potential early indication of a novel health threat, such as a zoonotic disease, industrial accident, or environmental threat. Similarity to a library signature may suggest a novel variant or previously unrecognized strain. The device thus can alert to new diseases or increased levels of a known disease (potentially preventing pandemics or epidemics) and/or novel variants. The system may initiate profiling the new disease based on a novel aberrant signature before the disease is publicly manifest.
The nanosensing elements comprise a VOC selective surface disposed atop a gated electronic chip. The selective surface interacts with proximal molecules to redistribute the sensor electron distribution and thereby to refocus the electronic properties across the nanosensing surface which alters the electronic properties (signal) of the chip output. In a preferred embodiment the chip has a base voltage underlying the sensing surface, a source electrode on the surface, a semi-conductor between the source and a drain electrode, and analytical hardware to detect, process and analyze electronic change events. The potential or the electromotive force between the source and drain electrodes is preferably between ~0.1 and 5V, more preferably designed in a rage about 1 - 3V. Higher voltages may be used, but these generally require higher quality or thicker chips to safeguard against interference. The chip current (flow from source to drain) is under control of the interaction between the nanosensing surface and nearby electronic influences. When a VOC shifts the interaction with the semiconductor bridge between the source and drain to increase conductance the increased current is detected and analyzed. The changes in current flow sensed by each
nanosensing element are monitored, collated and processed to identify disease specific patterns associated with these VOC interactions. The device preferably features one or more arrays of chips with each array outfitted with nanosensing elements designed to have different sensitivities, different affinities for different VOCs.
The sensitivity determinants on the nanosensing elements are molecules added as "decorations" or functionalyzing agents on the nanosensing element surface. These decorations will differentially attract (electronically react with) proximate VOCs. The time that a VOC lingers in close approximation with the nanosensing surface is one factor for recognizing a type of interaction. The magnitude of change is another. Time to peak value, slope of signal change (up and/or down), peak shape, over several differentially decorated sensing elements are available factors for defining the disease signature. Peak values or values averaged over time of the interaction (with a signal sensed in excess of a predetermined threshold value) are preferred factors for Al analysis in defining the disease signature patterns.
In a high discrimination mode, as the VOCs approach the nanosensing surface, a continuous recording of the interactions is analyzed. In instances where a single compound interacts with a sensing element, the VOC molecular configuration and/or orientation will change as it interacts with and is influenced by the nanosensing surface. This twisting or bending of the VOC can be a feature the device uses to recognize a specific VOC of interest. The high discrimination mode is not an essential feature of the device's functions. In preferred embodiments where a sensing array is configured with a plurality of differently functionalized nanosensing elements, not every sensing element will interact with every occurrence of a specific VOC in a sample. Multiple copies of each type of nanosensing element increases the probability of interactions between at least one nanosensor surface and the potentially relevant VOCs. The high discrimination mode is not a necessity for high- throughput screening practices.
The redundancy (multiple copies of the same sensor type) increases the sensitivity and selectivity of the device as many VOCs will bypass one or more nanosensing elements. The pseudorandom flow and geometry of the device mean that not every VOC will become proximate to every nanosensing element. Redundancy (multiple copies of similarly configured elements) allows averaging to reduce the random differences between samples.
The interaction between the proximate VOCS and nanosensing surface is transmitted through the sensing element to modulate current flow. The bias voltage and/or potential are set in the device and may be identical across all sensing elements, a subpopulation of sensing elements, such as a chip, a row, column, quadrant, or block on a chip, or individual elements on a chip. In high-throughput screening operations, referred embodiments simply use the same bias ans potential for all sensing elements.
The electronic sensing elements are controlled by a controller, preferably a digital to analogue converter that converts computer or algorithmic instructions to produce analogue voltages (potential) for the sensors. When the sensors are activated, analogue signals are outputted. An analogue to digital converter accepts the analogue signals and converter them to digital data that a computer analyzes, sorts, and stores. Hardware to collate and stream the data may be involved in the processing data for computer analysis. The computer may be on board, physically attached through an interface, or interfaced with a remote device.
When used in its preferred mode, that is, reading the off-gasses emitted from the underside or palm of a hand, the device is set for use in a real-time analysis seting, i.e., high-throughput screening for facility access. Gases are delivered from the person moving their hand over the device allowing the emited ambient gases to interact with the nanosensing element surfaces of the device. A negative pressure, device v. ambient, draws gases ambient to the sensor device through a port and across at least one sensing array of chips. As gases flow across and interact with the sensing surfaces electronic output data are obtained. These interactive data are collated and analyzed. The result is compared with one or more signatures associated with a disease or diseases. A match indicates that the device was exposed to emited gases associated with that disease or condition. When used for access control, the person whose VOCs matched a disease signature of interest is flagged for, e.g., denial of entry to a zone, direction to a positive match zone or location, additional screening, etc.
The device operates simply by receiving a gas sample from a subject source for analysis. The gas sample is preferable an easy to obtain personal offgas, such as from the palm of the hand. An exhaust fan configured in the device can provide a negative pressure that draws or intakes the ambient gases through an intake port into the device to flow over the
nanosensing elements. When a hand passes within few inches of the device entry port, vapors from the hand are included in these ambient gases.
An intake process may be activated by a timer, a heat activated switch, a motion activated switch, a light (or diminished light) activated switch, a voice or noise, an operator, etc. The device preferably includes an on/off switch that may be manually operated. A timer may increase flow for a specified collection time. A heat or motion activated switch may activate the device when a subject approaches or a hand is presented. An operator may control the operation manually, by voice, user interface, or other commands.
The electronic interactions sensed by the sensing elements are recorded and converted to a digital signal that is compiled and streamed to a data processor. The data are processed to produce a resulting pattern (profile) that can be compared to signature(s) for a disease of interest, to a select number of signatures associated with one or more disease of interest, or to a library of all disease associated signatures.
A disease of interest may be associated with a plurality of signatures. For example, an infectious phase and a resolution phase of a disease may be associated with different signatures. Different signatures indicative of a disease may be produced by persons presenting with one or more cofactors, for example, male or female, pregnancy, alcohol intoxication, fasting state, etc. The cofactor does not need to be identified prior to testing. Simply, the machine learning algorithms may have associated different signatures with the same disease under different cofactor conditions.
A library of VOC profiles and signatures associated with one or more selected diseases or conditions is produced for comparison with the subject's data that is produced by the device with each sample reading. The profiles and signatures held in the library of interest are developed using a machine learning or teaching process involving a selected group of subjects known to have symptoms associated with the disease or condition of interest and to have a confirmed diagnosis for the disease. Members of this group produce thousands of VOCs, many of which result from healthful biochemical reactions, but a fraction of which are particular by their presence, absence, concentration, or ratio with another compound or compounds, in a combination unique to the identified disease. The combination defines the signature for the associated disease. As the device tests additional samples, each definitive result may be used to strengthen or refine the library match process.
A group of subjects not identified with a particular disease may have their VOC results used as a negative disease control, i.e., indicative of VOC patterns that are not disease associated. When multiple disease signatures are of interest, the various disease groups can strengthen reliability by serving as negative controls for other diseases. Such "negative control" readings can serve as confirmation that an acceptable screening read has been completed. Subjects with a disease or condition other than that for which a signature is under development (Disease A) can serve as negative comparative controls for that signature. For example, a subject may be diagnosed with a condition such as prostate cancer, strep throat, cystic fibrosis, chronic fatigue syndrome, measles, Alzheimer's disease, gout, flu, bone fracture, hepatitis (A, B, C, D, E), lead poisoning, etc., but not Disease A.
These subjects can serve as negative controls for the learning set in developing a Disease A signature.
A preferred application of this invention is its use as a screening device for controlling access to a venue. A person is instructed with signs, video, and/or auditory instruction to place a hand over a port or screen on the device. When the hand position is acceptable and the emissions have been read, the person is instructed to move the hand away. Preferably a video or a set of cartoons will guide the subject to position the palm of the hand about 2-5 inches from the device sampling port. This movement of the hand may be adequate to deliver a sample from the person to the nanosensors and to produce the sample data for comparison to profiles or signatures in the library. Preferably, the palm off-gases are drawn through a port on the device surface to flow over the sensors. A sampling time ~2-5sec, preferably ~3sec, delivers the subject's VOCs to the device for analysis. Current computation time is about 3sec. A purge to clear that subject's VOCs from the sensor zone commences during the data processing and may continue until the next subject exposure. The subsequent exposure may be triggered, for example, by a temperature or motion sensor associated with the device. A purge time of 5sec supports a read rate of 7.5 subjects/min.
In most activations, the sensing elements report normal VOCs (those associated with the human species and not a particular disease or condition). An "AllClear"™ verbal or visual indication allows the subject to enter the venue. But when profiled VOCs are present the device can alert the subject stand aside or provide instructions to an attendant at the machine or along the venue entry pathway to deny entry or to instruct the person that
additional screening may be required. The additional screening may be on site or may require a delay (denial) for entry at that occasion.
As assurance the device is actively measuring VOCs for each subject encounter, the level of normal VOCs detected serves as an indicator that sufficient subject VOCs have been presented to the device. The device signals an AllClear™ when a threshold amount of VOCs have been read and no matching disease profile or signature has been observed. A timer may be set to terminate a sampling session when the threshold amount of VOCs has not been observed in a reasonable time. The exhaust/intake fan continues to pull ambient gas through the device to purge between subject samples. The purge flow may be set to a higher flow rate than that used in sample reading.
A completed test result that does not match a signature of a disease of interest is granted access. Such grant may be indicated by the AllClear™, a light, sound, or action such as a gate movement, indicative that the person does not express the disease of concern and can continue through the access portal. The clearance, e.g., an "AllClear™" notice, may be communicated in words or other recognizable output signal, for example, a green light, a progression of lights along a strip; a positive tone, chime, or RIF; a verbal confirmation or instruction; a gate opening; a gate not closing; a moving walkway; or seat activation; etc.
The signal indicating lack of positive match signal, may similarly be delivered by any acceptable means, e.g., light, barricade, sound, etc.
When the subject profile matches that of a disease of interest, the subject would be instructed to undergo additional assessment, perhaps taking off a glove or rubbing hands to stimulate circulation. A non-passing determination instruction or action may guide the person to secondary assessment or to seek further testing, deny entry entirely, restrict admittance to an alternate section, etc.
Secondary assessments may be provided in a number of formats. For example, they may require the subject to simply repeat the test a second time or to step into a separate line for a longer time analysis. The subject may be instructed to remove his or her gloves and present the hand for retest. Secondary assessments might also involve testing gases from another body part. A wand or hand held sniffer connected by an umbilical cord to the device or an alternate device may be used to draw a sample from ambient gas around a portion of the subject, e.g., the neck, armpit, forearm, leg, etc., and then to deliver the gas to the original device or to a dedicated secondary assessment device. The wand may briefly
store a sample for delivery to the device. In some embodiments, a wand may itself include nanosensors similar to those in the primary device, but rather than in a box shape, have nanosensing elements disposed in a rod or tube to collect samples from another body area, e.g., the back of the neck, the mouth expelling breath, an armpit, etc.
The device may use the wand as an adjunct sensing tool to be used for screening persons not able to deliver their samples to the sensing module. For example, a person may not have free use of a hand to present to the testing surface; assessing an amputee may require access to a body part other than a hand. An injury may make it impossible, painful, or inconvenient for a subject to present their hand to the device for screening. A toddler or infant may be in a backpack, stroller, carriage, etc., and thus unable to place its hand properly for screening. The wand acts as a tool allowing a device operator or a subject's colleague or guardian to direct the air collecting port in the wand at an alternate body part (or from a hand of a person who is unable to present it themself).
The tip of the wand is directed near the alternate source of the emitted gases. The wand may be in a continuous draw mode as it is guided towards the subject, it may start drawing in gases when moved, it may include a trigger or button to activate gas collection and delivery. The drawn gases continue through the wand to access the sensing chip(s) where the screening is effected, e.g., in the wand device or near or at an exit from the wand device.
The wand may be used as an adjunct test on non-humans, i.e., to assess object rather than persons. In customs, a disease carried on a parcel, bag, etc., carried by a person would serve as a subject for , e.g., farm borne diseases. An agent would merely point the wand to the area of targeted handbag, etc.
This preferred box shape embodiment would be available for use in a wide variety of placements. It may be set up at any angle, e.g., vertically, horizontally or any angle in between. The nanosensing elements of the device may be configured as a flat surface, flat surface surrounding a recessed area designated for receiving a hand, a curve, a ring, a closed or open shape to accept a hand or other body part - any shape that allows the test subject to deliver emitted off-gasses to the device sensing zones. The device may be designed and delivered for use in many applications including, but not limited to: a countertop, a turnstile, a wall or barrier defining a walkway, an arched entrance or exit, an escalator, an enclosure (cubical, booth, security scanner, dressing room, outfiting room, phone booth, elevator,
etc.), a tent for a meeting or show, a nightclub, a cabaret, a house of worship , a bar, a club, a bank, a cruise ship, a fraternity, a sorority, a funeral parlor, a birthing center, a train, an airplane, a frigate, a cruise ship, counter, a tourist attraction, a theme park, an aircraft carrier, a factory, a subway platform, a public conveyance, a tunnel, a dining room or cafeteria, a restaurant, a hallway, a zone, a secured area, a classroom, a hospital, a courthouse, a coliseum, a stadium, a military installation, an office building, a ferry, a jail, a prison, a voting location, a van, a mobile test site, a mall or retail establishment, a museum, a theater, a cinema, a library, a lobby, a waiting room, customs and immigration checkpoints, a detox center, convention centers, hotels, motels, warehouses, food processing facilities, agribusinesses, space stations, laboratories, etc., in essence any location where people pass through, meet, or congregate. As a person's hand or other body part, e.g., face, breath, etc., becomes proximal to the nanosensing module, gases are driven across the module and analyzed in real-time.
Different venues may incorporate additional features relevant to their missions. For example a concert venue may use the device in an embodiment that includes a ticket scanner, whereby a person seeking entry would require the ticket in addition to the VOC AllClear™ result for admittance. Other venues may wish to incorporate a physical ID reader, e.g., an RFID, a scanner, a bar code, QR code, palm print, fingerprint, facial recognition, or other personal identification to be checked against databases to confirm that the person has a need to enter, at the same time a person receives an AllClear™ designation. A primary application of this invention is for protection and safety of the traveling public which a fundamental component of commerce, both local and international. As such, municipalities, municipal authorities, etc. will benefit from the implementation the WAVE™ technology associated with the present device for use at airports, train stations, bus terminals, ferries, etc. As such local authorities will use this technology to expedite customer access and movement by combining multiple steps in the security, check-in, validation, etc., in combination with the health screening protocols. Devices that are operated by airlines with access to their Passenger Name Record (PNR) lists to guarantee the safety and security of their passengers and staff. These devices can be used for both departure and arrival. Upon arrival at the destination gate screening may be implemented or repeated to insure local authorities that infected passengers are not arriving in their jurisdictions. When interfaced with the passenger database, the departing passenger could be informed of the terminal or
gate of the flight, flight delays - if any, weather at the destination, boarding status, etc. At their destination, the passengers undergoing health screening may be informed of baggage information, connecting flights, messages relating to hotel, rental car, etc. A biometric ID check incorporated with the device may eliminate the need for paper documents, such as ID cards, tickets, boarding passes, baggage checks, etc.
In an office building, court house, or hotel lobby, the VOC scan incorporated with personal identification, may instruct the subject to a floor or room number and elevator to access the room and ask for a response whether help with baggage or any special treatment is needed. In a warehouse or factory, a separate punch clock would no longer be necessary. In a waiting room, entry and exit times may be recorded to validate that persons are served in order. A time flag may be built in when a subject fails to exit when expected to either search for that individual or remove them from the queue. In venues when a specific set of individuals is required for a function, the device at the time of access screening, can inform other participants of the additional arrival or last person to arrive.
Since assessing the VOCs from the palm is a primary preferred embodiment, the palm print or a portion thereof may be a preferred biometric in an associated reading device. The biometric ID check may interface with other databases, e.g., the Do Not Fly List, or other list and alert authorities for possible additional attention. The screening device with its optional adjuncts operates continuously with minimal operator input required. When incorporated with a gating system, the system controls access automatically. Personnel requirements associated with using the device are low allowing more efficient assignment for employees. Problems with employee alertness due to shift changes are minimized or avoided. Although the venue access screening primarily concerned with a communicable disease is a primary function of the device, use in combination with accessory sensors and database access improves access control and customer service while incorporating other tasks involving data obtained during a single scan or reading.
While assessment of metabolic diseases is a primary function of the device, the device may be programmed to operate in a mode where VOCs carried on an individual, an individual's clothing, a package, etc., may be monitored. This program mode looks at content of, or recent exposure to, possibly dangerous or hazardous molecules. These may include but are not limited to: explosives, explosive ingredients, explosive residue, toxins, environmental markers, etc. In the non-metabolic VOC operations, persons may for
example, be screened or cleared to exit an area zone that might have been associated with a release of a toxic substance.
While the device is designed for controlling admittance of individuals passing through a checkpoint, the device may be put to use for detecting presence of a condition or disease in a less controlled crowd situation. In a location where a crowd gathers or passes through, the device might not be targeted to screen individual subjects to prevent their entry, but perhaps to count the number of passersby presenting with a disease of interest or to a selected group of diseases. This application is particularly useful for public health officials when monitoring the introduction, spread or waning of one or more of the diseases including locations where disease spread is happening or is more likely. One example is a public transport system such as a subway where persons entering and exiting specific stations can be assessed, even anonymously. The primary sourcing stations and disease stations can be used for mitigating disease spread. Track and Trace is expedited by identifying major sources and locations of likely contact of the infected individuals with others at the locations of disease exit.
However formatted and applied, the device is or is part of a system that comprises: a control component, a sensing component, a data delivery component, an analytical component, an information storage component, and a reporting component. The primary sensors are nanosensing elements that monitor VOCs in real time. Other sensors in or associated with the device may include operational features including, but not limited to: an on/off switch, a WiFi or Bluetooth detector, a motion detector, a temperature sensor, a proximity sensor, a time sensor, a global positioning sensor, a light detector, a sound detector, etc. The primary sensors react to the electrical properties of a molecule in close proximity. Weak influences, attractive or repulsive result in a change in the electronic characteristics on the sensor surface. Different VOCs will influence and be influenced by the nanosensing surfaces. These changes or interactions will be repeatable for the same molecules closely approximating the sensor surface.
In a preferred configuration, multiple copies of similarly "decorated" sensors will be activated in an analysis. The decorations or functionalizing compounds interact with the VOCs. Aromatic, cyclic hydrocarbons and heterocyclic compounds frequently interact with a large variety of VOCs. Nucleic acids such as DNA strands are preferred functionalyzing compounds. The heterocyclic rings in the nucleic acids assist in securing the nucleic acid to
conductive surface on an electronic chip. Nucleic acids are also a preferred decoration because of their variability and ease of production. Different sequences of the four natural nucleotides, for example in a sequence with just eight nucleotides, provide over 4,000 available sequence structures to choose from. Longer strands provide better adhesion and more sequence structures to choose from. Using synthetic nucleotides in addition to the four, further increases the number of choices available.
Even though many sequences can interact with a given VOC, different decorations provide for differential interactions and thereby are tools for optimizing differentiation capacity, selectivity and sensitivity. Incorporating different decorations on different sensing elements in the device provides differential identification between two or more similar VOCs. In a refined embodiment, specific VOCs of interest have been identified and decorations selected to more selectively interact with those VOCs.
A preferred semiconductive surface on an electronic chip comprises elemental carbon. Single layer planes or tubes of carbon are especially advantageous for their retention of decorations such as biologic molecules, which contain a lot of carbon atoms, but also for compactness and capacity to transmit electronic fluctuations occurring as decorations are affected by proximal electronic (VOC) influences. Single layer two dimensional graphene may also be used in some embodiments by themselves or in conjunction with Single Wall carbon NanoTubes (SWNTs). Crumpling the graphene so that it does not lay flat can increase surface area and allow for 3-dimensional fiting of decoration molecules. SWNTs with their tubular carbon structure are a preferred carbon base for transmiting the current and adhering to the decorations. The carbon base, preferably formed with semiconducting SWNTs, is adhered to a dielectric chip surface, such as Hf02. A preferred density is about 50 nanotubes/linear micron (of ~3m) across a preferred nominal chip width of ~3-10m. Functionalized area 250 x 500 microns The nanotubes can be applied by bathing the nascent chips in SWNTs in toluene. But this method involves cumbersome masking etching and cleaning. SWNTs are delivered by the vendor in toluene. With each dip or bath, the concentration of nanotubes decreases. The nanotube coating from the first bath is different from the later batches. Array 4x4 =16 transistors 250x500. CNT covers all 16.
The preferred method of coating the chip surface avoids the nanotube density variability from first to last bath and does not require the masking, etching and cleaning steps. Nanotubes are precision applied to each sensing element. The chamber is fed toluene
IB
as a vapor or from a heated compartment containing toluene. The feed rate of toluene polymer wrapped 1.2-1.4 2 micron diluted with an inert gas or heat applied to the toluene compartment controls the toluene vapor pressure. The carbon nanotubes are misted through an atomizing nozzle to apply the carbon directly on the Hf02 surface between the source and drain electrodes. The toluene atmosphere is controlled at about to slow drying thereby allowing the nanotubes freedom to orient evenly on the surface thereby eliminating, reducing, or minimizing the coffee ring effect commonly observed with droplet drying.
The functionalyzing agents are then micro pipetted onto the carbon nanotube surfaces with controlled humidity, ~90%, to promote even drying and to avoid the coffee ring effect.
The Hf02 dielectric base underlying the current carrying carbon layer is preferably about 20-90nm thick. The Hf02 is preferably evenly spread using a process such as atomic layer deposition. A Hf02 coating, preferably about 30-50nm. More preferably ~40-45nm, sits atop an Al203 base on a standard chip, such as silicon dioxide. Al203 base supporting the Hf02 is preferably about 3-20nm, preferably deposited using chemical deposition of aluminum that is allowed to oxidize or atomic layer deposition.
The nanosensing elements can be of a variety of preselected sizes (areas, dimensions, diameters), heights (due to stacking density), shapes and configurations. Preferably, a nanosensing element SWNT surface is decorated with a single species of biomolecule, often a nucleic acid such as RNA or DNA with a length between 8 and 25 nucleotides. The SWNT interface surface on the chip' generally accept cyclic, especially polycyclic compounds, e.g., porphyrins, phthalocyanines, and azobenzene, as non-covalent associations on their surfaces. Polymers such as the nucleic acids, polyethylene glycol, and fatty acids - especially those conjugated with short polypeptides also form stable surface interactions with the single layered carbon structures and thus are available choices as functional groups on the nanosensing element surfaces. Modified nucleic acids with e.g., nucleotides other than the standard A, C, G, and T and/or incorporation of other molecules in the complex, e.g., stable nucleic acid lipid particles (SNALPS), offer additional choices for detection variations. The assembly of SWNTs decorated with such addons is well-known in the art. Therefore one skilled in the art does not require a repeated teaching in this paper. Preferred embodiments include chips and arrays that have several different functionalyzing decorations. Increased variability in surfaces that interact with the VOCs increases differentiation (selectivity)
capacity. Following a convention in the technological arts, devices with 8, 16, 32, 64. 128, 256, 512, 1024, etc., may be distributed as the technology gains acceptance and hardware decreases in cost.
The device may be configured as a circuit card or a collection of circuit cards. Each card supports a plurality of sensing elements both physically and interconnectively. A digital to analogue converter powers the nanosensing operations. Digital instructions are converted to dictate or influence analogue values, for example of temperature, bias voltage, gate voltage, etc., on the nanosensing elements. An analogue to digital converter accepts input from the nanosensing elements and produces digitized data. The data are organized and streamed by a controller of the outputted signals. Inputs from a plurality of simultaneous measurements, e.g., current fluctuations, are organized and combined in a stream of data for computer analysis. Interfaces that connect the different functions and components are provided.
A plurality of computers may be interfaced to work in or with the system. For example a NUC computer may process the sensor results in an on board operation. The on board computer may interface hard wired or remotely with one or more adjunct computers, e.g., at a testing station or remotely in a central collection and processing facility (e.g., for data security) or across outside computational support such as a "cloud" service vendor.
Power can be through a battery or remote delivery, that is provided by a source outside the main device cabinet. Power delivered through an external source is preferably delivered through a device battery to remove electrical noise. The outside power will often be delivered electrically through conductive cabling, but other means of power transmission, e.g., inductive pickup, light beam, solar panel, etc., can work as well. A gate voltage serves as differential that allows current to flow. The current flows, in response to alterations in a bias voltage that changes in response to electronic interactions between the VOC and the nanosensor and the nanosensor support. These voltages maybe under directions delivered through the digital to analogue converter.
A bias voltage may be selected as optimized depending on the nanosensing elements and supports chosen. A lOOmV to 2V bias is compatible with many devices. But the allowable range may span several orders of magnitude. For example bias voltages in the order of lOmV, lmV, 100pV, 10pV, lpV, or even in the nV range may find some applications. Similarly, bias voltages greater than lOOmV, e.g., in the order of IV, 10V, 100V, 1,000V may be useful in other applications.
A gate voltage ~1-5V modulates the source-drain current. A value of ~3V is easy to achieve and corresponds to two regular alkaline batteries. As capacitance is reduced, e.g., by reducing insulating layer thickness, the gate voltage may be reduced. The current flow is a design choice meaning that the direction of flow (changing voltage from plus to minus) depends on configuration choices. A voltage in the order 0.1V, 0.3V, IV, 5V, 9V, 12V, 18V,
20 V, 24V, 30V, etc., may be selected.
An exemplary nanosensing cartridge array may comprise an array of 256 nanosensing elements arranged in a 4 x 4, 8 x 8, or 16 x 16 grid. While each element or a selection fraction of elements, e.g., a 4 x 4, or 8 x 8 block, a column or a row, may be individually manufactured to have its unique decoration, the ease of manufacture and advantages of redundancy suggest building chips of: e.g., 256, 400, 512, 1024, etc. Individual sensing elements or groups of sensing elements may present with different temperature or bias voltages though on the singly decorated chip so not all elements will interact identically. Redundant sensing elements, sensing elements made to the same specifications are referred to as "sensing blocks." Use of blocks with a plurality of members can reduce response variability and allow continued operation when a nanosensing element malfunctions. A basic 4 x 4 sensing block renders 16 sensing blocks in a 256 chip array cartridge. A preferred arrangement has 16 different selective decorations, 1 for each sensing block. A device with 2 such cartridges presents with capacity for 32 different sensitivity modifications in 4 x 4 sensing blocks, with each such block accordingly having 16 copies with the same interactive surface molecule.
A circuit card holding a chip cartridge with multiple, e.g., 16 sensing blocks, can serve as an electronic component central to the sensing operations. For example, 256 element chips may be arranged in a 4 x 4, 4 x 8, 4 x 16, 2 x 4, 2 x 8, 2 x 16, or other selected geometry of 16, 8, 4, 32, 16, 32, sensing blocks, respectively. In some embodiments chips may be disposed on opposite sides (front and back, top and bottom) of a circuit card. The number of elements on a chip is a design choice. This example using 256 was chosen for its analogy to computer circuitry where powers of 2 are common. Continuing with this theme designers may prefer chips with 128, 512, 1024, 2048, 4096, etc., sensing elements. Incorporating sensing elements on both sides of a chip, e.g., top and bottom, is an obvious method for doubling. When chips are arranged in a square, a factor of 4 would be observed. However, the designer is not bound to follow these conventions, a chip with any convenient number
of sensors is possible, e.g., 25, 81, 625, etc., 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 51, 54, 57, 60, etc., 36, 49, 64, 100, etc. The sensor blocks on such chips need not be the same size. (the same number of elements. For example, a 256 element chip array might be configured as a 16 x 16 grid pattern (0-15 for column numbers and A-P for row numbers). 0-3:A-D might be a first sensor block of 16 elements decorated with nucleic acid nai. A second sensor block also of 16 elements at 4-ll:A-B might be decorated with nucleic acid na2; a third sensor block of 32 elements at 12-15:A-H might be decorated with nucleic acid na3; a fourth sensor block of 8 elements at 0-3:E-F might be decorated with nucleic acid na4; a fifth sensor block of 32 elements at 0-7:M-P might be decorated with nucleic acid na5; a sixth sensor block of 12 elements at 4-7:C-F might be decorated with nucleic acid na6; a seventh sensor block of 40 elements at 7-ll:C-J might be decorated with nucleic acid na7; an eighth sensor block of 32 elements at 0-15:K-L might be decorated with nucleic acid na8; a ninth sensor block of 32 elements at 8-15:M-P might be decorated with nucleic acid na9; a tenth sensor block of 2 elements at 15:I-J might be decorated with nucleic acid nai0; an eleventh sensor block of 40 elements at 7-ll:C-J might be decorated with nucleic acid nan; and a twelfth sensor block of 28 elements at 0-6:G-L might be decorated with nucleic acid nai2. A row or a column, a half row or half column, or other pattern can be configured as a a sensor block. The cards or arrays may be placed parallel or perpendicular to or at an angle off the sensing device surface port.
A designer may choose any convenient arrangement and number of chips on a card or in a device. For example, square arrangements of chips, 3 x 3, 4 x 4, 5 x 5, 6 x 6, 7 x 7, 8 x 8, 9 x 9, 12 x 12, 16 x 16, 32 x 32, etc., may be convenient. Columns of chips, e.g., 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 32, 64, etc., may be chosen for a rectangular arrangement. For such rectangular arrangements, the rows likewise can be of a number convenient to the designer.
In some configurations 4 cards may serve as box walls, with opposing sides of the box having sensor components facing one another. Since 1, 2, 3, or 4 sensor cards are sufficient with additional cards adding to redundancy, this style of disposition allows for the card or cards with the greatest signal (perhaps closest to the hand or closer to the tissue with best off-gassing) to signal data collection endpoints when a threshold of VOCs has been detected.
In embodiments with multiple cards, different cards may be optimized to detect different diseases or to operate at different temperatures. The activated card may be auto- selected, e.g., for ambient temperature, or remotely or locally selected for the disease of
interest. Pentagons, rectangles, hexagons, triangles, curved shapes, regular or irregular are suitable designs for housing the sensing components. Additional redundancy improves durability (time between maintenance) and has a valuable feature of allowing cross checking during calibration cycles. The number of sensors and separate sensor chips is therefore a design choice. If a single chip or even a single card appears faulty, the redundancy allows the device to continue operations. Redundancy is a design choice to be decided by the designer, manufacturer, purchaser, regulative body, etc.
The sensing circuit cards are not confined to box shaped disposition. The sensing plate or card may be situated on or recessed in a surface vertically or horizontally, e.g., in a countertop or railing as an example for assessing persons on a walkway or moving walkway. A zone adjacent to a doorbell or an elevator button may be outfitted with a sensing module. The device may be portable, i.e., available for a person to carry in a case. The device may be fixed in a building structure or as part of an entryway to a building or part thereof. A portable device may include attachments allowing vertical, horizontal or other angle disposition. Any flat or curved surface may be configured as a device retainer and therefore a screening location. When multiple sensor components are present, some may be arranged in a parallel orientation for simultaneous subject exposure, others may be arranged in series such that opportunity for exposure of the subject gases to the sensor components is along a time sequence.
The device is preferably programmable in one or more respects. A simple programming operation involves activating or turning on the device. The device is also controllable through the electronics and permitted access of gases to the sensors e.g., though a slide port. The sensors or data collection, analytical and/or storage functions may be under program control, for example, by operator interface, subject interface, motion, detection, time interval, a screening sensor that activates other sensing components or functions, a remote control, etc. The program may be selected from a collection of programs stored for the machine to select from. Programs may be delivered from a centralized location such as a company, home office, a local office, a security, room, an inserted instructional or datacard, etc. The interface carrying the program may feature a component including, but not limited to: a keyboard, a touchscreen, a chip (such as a USB chip) a microwave transmitter and receiver, a WiFi connection, Bluetooth, an e-pen, a port for plugging in a chip, a phone, connection, a computer, a computer memory and program storage device, an app on a
connected or remote electronic device, a dedicated tap and touch pad or screen, a microphone with voice deciphering capability, biometric security modules (e.g., face recognition, voice recognition, fingerprint, keyboard patterns, etc.). Additional security may include features including, but not limited to: access coding from a person or machine, encryption, confirmation required by a system manager, etc.
The programming may be as simple as activating the device or a portion thereof. The programming may select one or more diseases for matching. The programming may incorporate additional learning cycles. The programming may interactively adjust one or more sensor's parameters such as adjusting temperature, a voltage, a weighting applied to a sensor's or a group of sensor's outputs, a screen that may divert gas or direct the gas more strongly at a particular sensor or group of sensors.
The device is adaptable and programmable for application in different environments or applications. Outdoors or in environments with flow, a windscreen may be affixed on the device to facilitate capture of subject emitted gases by shielding the zone surrounding the sensing area from convection currents that may convey the VOCs past or away from the sensing elements. Lighting may help direct the subject to the test device and/or direct the subject how and where to place or move the hand. Light intensity may be increased for dimly lit access areas or for outdoor use at night.
Disease libraries with their profiles and/or signatures can be added or deleted as concern for a disease grows or wanes. Program updates may be frequent for some diseases as variants change prevalence. Emerging diseases, such as COVID-19 in the early 2020s, can be incorporated in the programming as the disease becomes recognized. Different venues may feature different programming. For example, a positive test at some venues may simply advise the subject and deny entry. In a different venue, an escort may be summoned to guide the subject for further assessment or treatment.
The programming in a particular device may direct comparison to a single disease or condition of interest, to a select group of diseases, to diseases with associated signatures, to a set of toxins, or other comparisons selected by the user. Program updates to add or adjust profiles or signatures can keep the device current. Programming may be effected using any acceptable interface or interface method. Programming may require a hardwired or plug in device when strict control is observed. Wireless updates may be accomplished automatically or on request.
While the the methods related to using the device to recognize signature patterns of diseases do not require identification of the molecular structure of the VOCs or other compounds detected, knowledge of specific molecules that are involved in a disease signature can act as a factor in improving the device. Identifying the compounds instrumental in forming the disease signatures can be applied to, e.g., selecting a decoration or decorations for the sensing elements, adding scavenger compounds to differentiate between similar compounds, adjusting a voltage or temperature, adding a pre-read filter, etc. For example, time for evaluating each subject sample, sensitivity and/or selectivity of the device, may be refined by chemical analysis, including, but not limited to: x-ray fluorescence spectrometry, ion chromatography, gas chromatography, gas chromatography- mass spectrometry, inductively coupled plasma mass spectrometry, inductively coupled plasma optical emission spectroscopy, scanning electron microscopy, x-ray diffraction, electron probe microanalysis, nuclear magnetic resonance, etc.
In analogous applications, the device may be programmed to screen objects passing by on a belt . The device itself be motile to pass by or over objects of interest. The wand/umbilical tube embodiment may be used in this manner for example as a tabletop mount, a portal mount, a belt mount, a chest or backpack mount. Controls may be incorporated into the wand itself or in the sensing module of the device. The operator may target the exterior in general, one or more parts of an item, e.g., a seam, an opening, a taped area, etc. An open or broken container may be tested to determine degree of hazard to handlers or the public. The programming may be installed in a device to allow switching between detection targets. The device may be configured for a select group of detection targets. Programming for modes not originally installed in the device or accessible to the device may be added using a contact, e.g., plug-in connection, or may be delivered through remote transmission.
The device may be part of a system of devices where the experiences of each device are delivered into a cloud or other inclusive data set. The system continues to analyze the data and notifies device operators when updates are available or when instructed by the operator or in concert with regulations delivers downloads to the relevant devices. Additional assessments may involve a screen that does not involve VOCs as tested by the device, including, but not limited to: a biosample (e.g., PCR or antigen), a thermal reading, an x-ray, etc.
Claims
1 A molecule sensing device comprising: a) a sensor component comprising a plurality of sensing elements on a sensing chip with sensing elements that alter an electronic signal in the presence of volatile organic hydrocarbons (VOCs); b) a digital to analogue converter for converting digital instructions to analogue bias voltages and gate voltages; c) an analogue to digital converter for converting sensing element signals to digital output signals from at least one of said plurality sensing elements; d) a controller for accepting and streaming said converted digital output signals; and e) a computer interface at the output end of said controller.
2. The molecule sensing device of claim 1 wherein said sensing elements comprise: al) carbon nanotubes adhered to a hafnium oxide dielectric; and a2) a decoration adhering to said carbon nanotube.
3. The molecule sensing device of claim 2 wherein said decoration comprises a polymer of nucleotides.
4. The molecule sensing device of claim 3 wherein said polymer comprises a DNA.
5. The molecule sensing device of claim 4 wherein said polymer comprises an RNA.
6. The molecule sensing device of claim 1 wherein a potential between a source and drain electrode is in a range of about 0.1 to 5V.
7. The molecule sensing device of claim 6 wherein a potential between a source and drain electrode is in a range of about 1 - 3V.
8. The molecule sensing device of claim 3 wherein close association between a VOC and said polymer decoration increases current through said carbon nanotubes.
9. The molecule sensing device of claim 2 wherein said plurality of sensing elements comprise a first sensing element with a first decoration and a second sensing element with a second decoration and wherein said first and said second decorations are different.
10. The molecule sensing device of claim 9 further comprising additional different sensing elements and corresponding additional decorations.
11. The molecule sensing device of claim 10 wherein the totality of different sensing elements and decorations comprises a sum equal to or in excess of eight.
12. The molecule sensing device of claim 11 wherein the totality of different sensing elements and decorations comprises a sum equal to or in excess of eight.
13. The molecule sensing device of claim 12 wherein the totality of different sensing elements and decorations comprises a sum equal to or in excess of sixteen.
14. The molecule sensing device of claim 1 comprising at least 28 sensing elements.
15. The molecule sensing device of claim 1 comprising at least 29 sensing elements.
16. The molecule sensing device of claim 1 comprising at least 210 sensing elements.
17. The molecule sensing device of claim 1 further comprising interface with a memory bank retaining at least one signature of interest.
18. The molecule sensing device of claim 17 wherein said onboard computer comprises said memory bank.
19. The molecule sensing device of claim 18 wherein said computer circuitry has capacity to compare a signature or profile read by said molecule sensing device with at least one signature in said memory bank.
20. The molecule sensing device of claim 17 wherein said interface interfaces with a data storage module at a remote location.
21. The molecule sensing device of claim 1 further comprising a hard wire plug in interface to said digital to analogue converter.
22. The molecule sensing device of claim 1 further comprising a digital memory that comprises programming instruction that controls one or more device functions.
23. The molecule sensing device of claim 22 wherein said digital memory is programmable.
24. The molecule sensing device of claim 23 wherein said digital memory is programmable through a remote interface.
25. The molecule sensing device of claim 1 disposed in a vertical orientation.
26. The molecule sensing device of claim 1 disposed in a horizontal orientation.
27. The molecule sensing device of claim 1 wherein said sensor component is covered by a hand shaped recess.
28. The molecule sensing device of claim 1 comprising a plurality of sensor components.
29. The molecule sensing device of claim 28 wherein at least two of said plurality of sensor components face one another.
BO. The molecule sensing device of claim 28 wherein at least two of said plurality of sensor components are disposed in series along a path such that a subject passes them in sequence.
31. The molecule sensing device of claim 1 further comprising a gas delivery feature whereby gas is harvested through a tubular structure for presenting to said sensing chip.
32. The molecule sensing device of claim 1 further comprising a feature that accesses a personal identification for a subject undergoing the sensing.
33. The molecule sensing device of claim 2 wherein said Hf02 is a dielectric about 20-90nm thick.
34. The molecule sensing device of claim 33 wherein said Hf02 is a dielectric about 40-45nm thick.
35. The molecule sensing device of claim 33 wherein said Hf02 is a dielectric over an aluminum oxide layer in a range about 3-20nm thick.
36. The molecule sensing device of claim 9 comprising a plurality of each of said first sensing element and said second sensing element.
37. The molecule sensing device of claim 36 wherein said pluralities features at least 8 of each sensing element.
38. A method of applying a coating on a surface between a source and a drain electrode to the molecule sensing device of claim 2, said method comprising: controlling evaporation rate of a carrier liquid within said chamber during a said coating deposition event.
39. The method of claim 38 comprising, in a chamber containing a chip to be coated with carbon nanotubes: controlling the vapor pressure of toluene in said chamber to between about 75% and 95% of saturation; and misting a liquid comprising toluene and single wall carbon nanotubes through a nozzle directed at a said sensor surface to apply said coating interface.
40. The method of claim 39 further comprising: controlling relatiove humidity in said chamber to about 90%; and micropipetting a liquid comprising water and functionalizing molecules onto said sensor surfaces.
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