Patent Application
20220091011
This invention relates to methods of detecting biological particles, such as bacteria and viruses.
Many human and animal diseases are caused by infectious agents such as viruses, bacteria, fungi, prions, and parasites. In order to limit the spread of these diseases, it is often useful to identify infected individuals, so that precautions can be taken to limit their risk of transmitting the infection to others. For example, once an infected person is identified, they may be able to seek treatment for the disease, which may for example reduce the amount of time that they remain infectious. They may also be able to engage in practices such as social distancing to reduce their risk of transmitting the disease to others.
The applicant has appreciated a number of limitations and disadvantages of prior art methods of identifying infected individuals. For example, many tests for infectious diseases are expensive, complex, invasive and/or time intensive. These disadvantages of prior art methods can significantly reduce their capacity to rapidly identify infected individuals. For example, the nose swab tests used to test for COVID-19 have in many jurisdictions been in short supply, have been prohibitively expensive, and/or have suffered from significant time delays before test results are received. These limitations have likely contributed to the rapid spread of the virus in many jurisdictions.
A further limitation of the prior art is that typically individuals are only tested for a disease after they have developed symptoms. As many infectious diseases are contagious before the onset of symptoms, an infected individual may be infectious for a significant period of time before they are ultimately tested, during which time they may spread the disease to others. In some cases, contagious individuals may remain asymptomatic or may only develop mild symptoms, and thus never get tested. In many cases, the available test is too expensive, complex, and/or labor or time intensive for widespread testing to be offered to asymptomatic individuals.
An additional limitation of the prior art is that tests are typically designed to detect a specific, previously known disease or disease causing agent. As such, in order to screen individuals for a variety of different possible infections, several different tests would need to be administered, each of which may be expensive, complex, time intensive, resource intensive, and/or labor intensive. For this reason, widespread screening of a large population for a wide variety of different possible infections may not be feasible. Furthermore, many existing tests may be unable to detect novel diseases, such as new viruses that cross over into human populations from an animal host. This inability to test for novel diseases may prevent public health authorities from rapidly recognizing when a new disease is present in a population, and may hinder efforts to contain the spread of the disease.
To at least partially overcome some of the disadvantages of previously known methods and devices, in one aspect the present invention provides a method comprising passing a fluid through a negative sorting device that produces a negatively sorted stream of the fluid from which particles present in the fluid that are above a threshold size have been removed, and analyzing the negatively sorted stream to obtain a measure of a concentration of particles of interest in the negatively sorted stream. The applicant has appreciated that negatively sorting a fluid to remove particles that are larger than a particle of interest, such as a virus or a bacteria, can preferably allow the particle of interest to be detected without requiring the particle of interest to be directly manipulated or sorted.
The applicant has appreciated that a microfluidic particle sorter can advantageously be used to produce the negatively sorted stream in at least some preferred embodiments of the invention. It is known that microfluidic channels can be used to separate and concentrate particles in a fluid according to their size. See for example F. J. Cruz and K. Hjort, “High pressure inertial focusing for separation and concentration of bacteria at high throughput” 20171 Phys.: Conf. Ser. 922 012001; and Cruz et al., “Inertial focusing with sub-micron resolution for separation of bacteria” Lab Chip, 2019, 19, 1257, which are incorporated herein by reference. A known limitation of microfluidic particle sorters is that, as the size of the target particle decreases, the fluid pressure required to operate the system rapidly increases. This limits the usefulness of the known technology for sorting very small particles, such as particles smaller than 1 micron.
The applicant has advantageously appreciated that a microfluidic particle sorter can be used for the detection of small particles of interest, such as viruses, without requiring the particles of interest to be focused or positively sorted by the microfluidic particle sorter. For example, the microfluidic particle sorter can be configured to focus or positively sort particles larger than the particle of interest into a first stream or channel, and to direct the remaining fluid, from which the larger particles have been removed, into a second stream or channel. The applicant has advantageously appreciated that, if the small particles of interest are not focused or positively sorted by the microfluidic particle sorter, they will preferably remain dispersed throughout the fluid, and will be present in both the first stream containing the larger particles, as well as the second stream from which the larger particles have been removed. The second stream can then preferably be analyzed to obtain a measure of the concentration of the particles of interest in the fluid.
Advantageously, since the second stream does not contain the larger particles that were directed into the first stream, the analysis of the second stream can be performed using techniques that do not or are unable to reliably distinguish between the particles of interest and the larger particles. This preferably allows the analysis to be performed in a simple and cost effective manner. The analysis may be performed using any technique and/or apparatus that is suitable for obtaining a measure of the concentration of the particles of interest, such as for example electrical, acoustic, optical, magnetic, spectroscopic, chemical, and/or electromagnetic methods. The analysis may for example use a simple measurement of the electrical impedance of the second stream to obtain a measure of the concentration of the particles of interest in the second stream. In contrast, if the second stream contained both the particles of interest and the larger particles, then a much more sophisticated and complex analysis may be required to distinguish between the particles of interest and the larger particles.
A further advantage of at least some embodiments of the present invention is that, since the method preferably relies on negative sorting to produce the second stream (i.e. removal of the larger particles, rather than manipulation of the smaller particles of interest), the microfluidic particle sorter can preferably be operated at a lower pressure than would otherwise be needed to focus or positively sort the particles of interest. This preferably allows the apparatus performing the method to be relatively simple, low cost, and small, without for example requiring components that can generate and withstand very high pressures.
The applicant has appreciated that the invention may be particularly advantageous for detecting infectious biological particles, such as viruses. For example, the method could be used to screen individuals for signs of a possible infection, by negatively sorting and analyzing fluid collected from the individual. The fluid could, for example, be water that has contacted the individual's body, such as by being swished in their mouth or dispensed onto their hands. Preferably, the microfluidic particle sorter is configured to produce a negatively sorted stream that will contain any viral particles present in the fluid, with larger particles such as bacteria and skin cells being sorted into a separate stream or streams. A measure of the concentration of viral particles in the fluid can then be obtained by analyzing the negatively sorted stream.
In some embodiments of the invention, the presence of any particles in the negatively sorted stream may be used as an indication of a possible infection. If a possible infection is detected, action can then be taken to reduce the risk of the individual transmitting the infection to others. For example, an individual identified as having a possible infection could be directed to self-isolate or practice social distancing. They could also be directed to take another more specific test, such as a COVID-19 PCR test, to determine whether they may be infected with a particular pathogen of concern. The method can thus be used to pre-screen individuals for possible infections in a manner that is preferably low cost and fast, and which assists in identifying those individuals that should receive a more complex, expensive, and/or time and labor intensive test for a specific pathogen.
In one preferred embodiment of the invention, the method is performed using a hand cleaning fluid dispenser. The dispenser preferably dispenses hand cleaning fluid onto a user's hand, at least some of which is then collected for analysis to detect the presence of a virus or other pathogen on the user's hand. The fluid may, for example, be collected by a drip tray located below the user's hand, which collects excess fluid or overspray that drips off of the user's hand. The fluid is then directed to a negative sorting device, such as a microfluidic particle sorter, for example by a fluid pump. The negatively sorted stream is then analyzed for signs of a possible infection in the manner as described above. If a possible infection is detected, the user may be notified for example by a flashing red light on the dispenser. The user can then seek medical attention, seek testing for a specific pathogen of concern, self-isolate, or take other actions to reduce the risk of transmitting the infection to others, either voluntarily or under the direction of public health authorities.
Advantageously, hand cleaning fluid dispensers are widely available in many locations, including most washrooms and throughout many facilities such as hospitals and long term care homes, and are frequently used by many individuals. Adapting hand cleaning fluid dispensers to perform the method of the present invention would thus preferably allow for the wide-spread screening or pre-screening of a large number of individuals for possible infections, including pre-symptomatic and asymptomatic individuals.
The relative simplicity of at least some preferred embodiments of the invention, including the ability to operate at relatively low pressures and use relatively simple analytic techniques, preferably allows the method to be performed using small and relatively low cost components that can be incorporated into a hand cleaning fluid dispenser without adding too much complexity or expense. Dispensers capable of performing the method can thus preferably be made widely available.
In one preferred embodiment, the method includes compiling data from a large number of dispensers at different geographic locations. This data can then be used to establish a measure of the prevalence of infections in the different geographic locations over time, which can in turn be used to inform public health decisions. For example, if the fluid dispensers in a particular location, such as a hospital or city, are reporting an increase in the number of virus-size particles present on people's hands, then public health authorities may decide to increase testing for a pathogen of concern in that area, provide warnings to practice social distancing in that area, or take other actions to reduce the risk of disease transmission.
Advantageously, since the method of the present invention is preferably not limited to the detection of one specific pathogen or virus, it is preferably capable of detecting at least some novel pathogens before a specific test for that pathogen has been developed. For example, if a novel virus were to pass from an animal host into a human population, fluid dispensers performing the method of the present invention would preferably be capable of detecting the presence of the novel virus on people's hands. This information could then be used to take action to reduce the spread of the virus, such as directing possibly infected individuals to self-isolate. Public health authorities could also preferably use the data to rapidly identify and investigate infections as they emerge and spread through the population, including both novel and previously known viruses, so that appropriate action can be taken to protect public health. The method can thus preferably be used to provide an early warning of an infection or infections spreading through a population.
Optionally, data regarding the concentration of particles of interest in the tested fluid may be used in conjunction with other data. For example, the fluid dispensers could be equipped with infrared temperature sensors that sense the temperature of the user's hand to detect possible signs of fever. An analysis to establish a measure of the likelihood that the user has an infection could then be performed using both the concentration data and the temperature data. Data from other sources could be used as well. For example, data from an activity tracker such as a Fitbit™ smartwatch worn by the user could be collected wirelessly by the dispenser or an associated computer or server, such as via Bluetooth™ or Wi-Fi™. The collected data may include, for example, information about the user's biological functions or characteristics, such as heartrate, blood pressure, respiratory function, and blood-oxygen levels, as well as activity levels, location data, and travel history. This additional information may be used to further improve the assessment of the likelihood that the user has an infection. Optionally, the dispenser could be configured to transmit a warning that the user may have an infection to the user's smartwatch or mobile device to be displayed to the user on the smartwatch or mobile device. The smartwatch or mobile device could also receive and display warnings to avoid particular geographic locations where the risk of infection has been determined to be high.
In at least some preferred embodiments, the present invention is believed to be particularly well suited for detecting viral infections. One reason for this is that the mere presence of viral particles on a person's hands or other body parts may in at least some circumstances provide a strong indication that the person has a viral infection. This is because a person would generally not be expected to have any significant quantity of viral particles on their body unless they have a viral infection. As such, detecting any viral particles in the negatively sorted stream can be used in at least some embodiments of the invention as a strong indication that the individual has a viral infection. Optionally, the assessment of the likelihood that a person has a viral infection could be performed by comparing the measure of the concentration of particles of interest in the sample fluid to a baseline. The baseline could, for example, be the measure of the concentration of particles of interest that is obtained from a fluid that is known to contain no viral particles, or from a fluid that is known to come from a person who is not infected with a virus.
Optionally, any change in the measure of the concentration of the particles of interest in the sample fluid as compared to the measure of the concentration of the particles of interest in the baseline that suggests an increase in the concentration of the particles of interest in the sample fluid as compared to the baseline could be used as an indication that the person likely has an infection. Alternatively, the magnitude of the change in the measure of the concentration of the particles of interest as compared to the baseline may be required to reach some predetermined threshold before the person is identified as likely to have an infection. In either case, it is not necessary to determine the actual concentration of the particles of interest in the negatively sorted stream. Rather, all that is required is a detectable change in the measure of the concentration of the particles of interest as compared to the baseline. For example, if the particles of interest are known to reduce the electrical impedance of the fluid as the concentration of the particles of interest increases, then a measurable reduction in the electrical impedance of the sample fluid as compared to the baseline may be used as an indication that there is a greater concentration of the particles of interest in the sample fluid than in the baseline.
The invention may also optionally be used to detect other types of infections, such as bacterial infections. For example, the microfluidic particle sorter could be configured to sort out and separate larger particles such as skin cells, while leaving bacteria cells unsorted and thus present in the negatively sorted stream. The negatively sorted stream could then be analyzed to obtain a measure of the concentration of bacteria cells in the fluid.
A complication of using the method for detecting bacterial infections is that bacteria are normally present on the human body, even in the absence of an infection. As such, merely detecting the presence of bacteria on a person's skin normally would not be expected to provide a reliable indication that the person has a bacterial infection. However, changes in the quantity and/or type of bacteria present on the skin may provide an indication of a bacterial infection in some circumstances. As such, comparing the measure of the concentration of particles of interest in a sample fluid as compared to a baseline may in some circumstances be useful for assessing whether a person may have a bacterial infection.
The method of the present invention could also optionally be used to detect the presence or quantity of bacteria on surfaces that should have no bacteria or only a small quantity of bacteria on them. For example, when preparing or packaging certain food products, it may be desirable for the food products to have no bacteria present thereon or only a very small quantity of bacteria. By contacting the food product with a fluid such as water, and then processing and analyzing the fluid in accordance with the present invention, the presence of bacteria on the food product can preferably be detected. If the food product is found to have an unacceptable level of bacterial contamination, the product can then be sent for further testing, cleaning, or disposal, for example.
The method of the present invention is not limited to performing an analysis on the negatively sorted stream only. Rather, focused or positively sorted streams could be analyzed as well, in addition to or in place of the analysis of the negatively sorted stream. For example, if the microfluidic particle sorter is configured to sort bacteria into a focused stream while allowing smaller viral particles to remain unfocused or unsorted, an analysis could be performed on both the negatively sorted stream and the focused stream. The negatively sorted stream could be analyzed as described above to obtain a measure of the concentration of viral particles in the fluid, and the focused stream could also be analyzed to obtain a measure of the concentration of bacteria in the fluid. The focused stream could be analyzed by any suitable method, including for example by electrical, acoustic, magnetic, spectroscopic, chemical, optical and/or electromagnetic techniques. If the concentration of bacteria in the focused stream is found to be higher than in a comparison baseline, this may for example provide an indication of a possible bacterial infection.
Optionally, the particle sorter could be configured to sort a variety of different particles into different streams based on their size, shape, and/or other properties. A measure of the concentration of particles in some or all of the streams could then be obtained, to look for possible signs of infection or relevant contamination. For example, the sorter could be configured to sort bacteria having different sizes and/or shapes into different streams. If the concentration of bacteria in one of the streams increases as compared to a baseline, this could provide an indication of a possible bacterial infection. Since the size and/or shape of the bacteria is preferably known, in some circumstances it may be possible to identify the type or types of bacteria that are most likely to be causing the infection. This information may be useful for a variety of different purposes, such as assisting medical personnel in assessing what types of further tests may be needed, for prescreening individuals for a particular pathogen of concern, and/or for providing an early warning sign of an infectious disease spreading through a population.
Accordingly, in a first aspect the present invention resides in a method comprising: passing a fluid through a negative sorting device that produces a negatively sorted stream of the fluid from which particles present in the fluid that are above a threshold size have been removed; and analyzing the negatively sorted stream to obtain a measure of a concentration of particles of interest in the negatively sorted stream; wherein the particles of interest have a size that is less than or equal to the threshold size.
In a second aspect, the present invention resides in a method, which optionally incorporates one or more features of the first aspect, wherein the negative sorting device comprises a microfluidic particle sorter that produces at least one focused fluid stream and at least one unfocused fluid stream; wherein the microfluidic particle sorter directs the particles present in the fluid that are above the threshold size into the at least one focused fluid stream; and wherein the at least one unfocused fluid stream comprises the negatively sorted stream.
In a third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first aspect and the second aspect, wherein the particles of interest, if present in the fluid, are present in both the at least one focused fluid stream and the at least one unfocused fluid stream.
In a fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to third aspects, wherein the microfluidic particle sorter is unable to focus the particles of interest because the size of the particles of interest is too small.
In a fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fourth aspects, wherein the microfluidic particle sorter is operated at a fluid pressure that is too low to focus the particles of interest.
In a sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifth aspects, wherein the particles of interest comprise a biological particle.
In a seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixth aspects, wherein the particles of interest comprise a bacterial particle.
In an eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventh aspects, wherein the particles of interest comprise a viral particle.
In a ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighth aspects, wherein the particles of interest comprise an infectious agent.
In a tenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninth aspects, wherein the size of the particles of interest is less than 10 microns.
In an eleventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to tenth aspects, wherein the size of the particles of interest is less than 5 microns.
In a twelfth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eleventh aspects, wherein the size of the particles of interest is less than 3 microns.
In a thirteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twelfth aspects, wherein the size of the particles of interest is less than 1 micron.
In a fourteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirteenth aspects, wherein the size of the particles of interest is less than 0.8 microns.
In a fifteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fourteenth aspects, wherein the size of the particles of interest is less than 0.5 microns.
In a sixteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventeenth aspects, wherein the size of the particles of interest is less than 0.3 microns.
In a seventeenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixteenth aspects, wherein the threshold size is between 10 microns and 0.3 microns.
In an eighteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventeenth aspects, wherein the threshold size is about 1 micron.
In a nineteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighteenth aspects, wherein the threshold size is less than 1 micron.
In a twentieth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to nineteenth aspects, wherein the threshold size is about 0.8 microns.
In a twenty first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twentieth aspects, wherein the threshold size is less than 0.8 microns.
In a twenty second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty first aspects, wherein analyzing the negatively sorted stream comprises performing an analytic technique that, if the negatively sorted stream contained the particles above the threshold size, would be unable to reliably obtain the measure of the concentration of the particles of interest in the negatively sorted stream.
In a twenty third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty second aspects, wherein analyzing the negatively sorted stream comprises at least one of: optically analyzing the negatively sorted stream; electromagnetically analyzing the negatively sorted stream; acoustically analyzing the negatively sorted stream; thermally analyzing the negatively sorted stream; magnetically analyzing the negatively sorted stream; fluid-mechanically analyzing the negatively sorted stream; and electrically analyzing the negatively sorted stream.
In a twenty fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty third aspects, wherein analyzing the negatively sorted stream comprises measuring an electrical impedance of the negatively sorted stream.
In a twenty fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty fourth aspects, wherein analyzing the negatively sorted stream comprises comparing the electrical impedance of the negatively sorted stream to a comparison electrical impedance value.
In a twenty sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty fifth aspects, wherein the comparison electrical impedance value comprises a known or estimated electrical impedance of the fluid when the fluid contains none of the particles of interest.
In a twenty seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty sixth aspects, wherein the comparison electrical impedance value comprises a known or estimated electrical impedance of the fluid when the fluid contains a baseline concentration of the particles of interest.
In a twenty eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty seventh aspects, wherein the baseline concentration of the particles of interest comprises a known or estimated concentration of the particles of interest in the fluid when the fluid is prepared under a baseline condition.
In a twenty ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty eighth aspects, wherein the baseline condition comprises an absence of an infection in an individual from which the fluid is obtained.
In a thirtieth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to twenty ninth aspects, wherein the comparison electrical impedance value comprises a known or estimated electrical impedance of the fluid when the fluid contains a target concentration of the particles of interest.
In a thirty first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirtieth aspects, wherein the target concentration of the particles of interest comprises a known or estimated concentration of the particles of interest in the fluid when the fluid is prepared under a target condition.
In a thirty second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty first aspects, wherein the target condition comprises a presence of an infection in an individual from which the fluid is obtained.
In a thirty third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty second aspects, wherein the fluid is less polar than pure water.
In a thirty fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty third aspects, wherein the fluid comprises an alcohol.
In a thirty fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty fourth aspects, wherein the fluid comprises water.
In a thirty sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty fifth aspects, wherein the fluid comprises at least 50% alcohol.
In a thirty seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty sixth aspects, wherein the fluid comprises ethanol, isopropanol, or a combination of ethanol and isopropanol.
In a thirty eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty seventh aspects, wherein the fluid comprises a hand cleaning fluid.
In a thirty ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty eighth aspects, the method further comprising at least one of: collecting the fluid from a body of a human or an animal; and placing a sample in the fluid, the sample containing particles collected from an object, an organism, or an environment.
In a fortieth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to thirty ninth aspects, the method further comprising: contacting the fluid with a surface; and directing the fluid to the negative sorting device after the fluid has contacted the surface.
In a forty first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fortieth aspects, wherein the surface comprises an internal surface or an external surface of a human body.
In a forty second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty first aspects, wherein analyzing the negatively sorted stream comprises optically detecting particles in the negatively sorted stream.
In a forty third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty second aspects, wherein analyzing the negatively sorted stream comprises: obtaining an optical image of the fluid in the negatively sorted stream; and analyzing the optical image to count, calculate, or estimate a quantity of the particles of interest in the optical image.
In a forty fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty third aspects, the method further comprising: establishing a measure of a likelihood that an infection is present in at least one of: an organism, an environment, a building, a room, a person, and a group of people, based at least in part on the measure of the concentration of the particles of interest in the negatively sorted stream.
In a forty fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty fourth aspects, wherein establishing the measure of the likelihood that an infection is present comprises: repeatedly passing samples of the fluid obtained at different times through the negative sorting device; for each of the samples of the fluid, analyzing the negatively sorted stream to obtain the measure of the concentration of the particles of interest in the negatively sorted stream; and determining whether the measure of the concentration of the particles of interest in the negatively sorted stream has changed over time.
In a forty sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty fifth aspects, wherein establishing the measure of the likelihood that an infection is present comprises comparing the measure of the concentration of the particles of interest in the negatively sorted stream to a comparison measure of the concentration of the particles of interest in the negatively sorted stream.
In a forty seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty sixth aspects, wherein the comparison measure of the concentration of the particles of interest in the negatively sorted stream comprises a known or estimated measure of the concentration of the particles of interest in the negatively sorted stream when the fluid contains none of the particles of interest.
In a forty eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty eighth aspects, wherein the comparison measure of the concentration of the particles of interest in the negatively sorted stream comprises a known or estimated measure of the concentration of the particles of interest in the negatively sorted stream when the fluid is prepared under a baseline condition.
In a forty ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty eighth aspects, wherein the baseline condition comprises an absence of an infection in at least of: a comparison organism from which the fluid is obtained, a comparison environment from which the fluid is obtained, a comparison building from which the fluid is obtained, a comparison room from which the fluid is obtained, a comparison person from which the fluid is obtained, and a comparison group of people from which the fluid is obtained.
In a fiftieth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to forty ninth aspects, wherein the comparison measure of the concentration of the particles of interest in the negatively sorted stream comprises a known or estimated measure of the concentration of the particles of interest in the negatively sorted stream when the fluid is prepared under a target condition.
In a fifty first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fiftieth aspects, wherein the target condition comprises a presence of an infection in at least of: a comparison organism from which the fluid is obtained, a comparison environment from which the fluid is obtained, a comparison building from which the fluid is obtained, a comparison room from which the fluid is obtained, a comparison person from which the fluid is obtained, and a comparison group of people from which the fluid is obtained.
In a fifty second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty first aspects, the method further comprising: dispensing the fluid onto a hand of a person; collecting the fluid after the fluid has contacted the hand; and directing the fluid to the negative sorting device after the fluid has contacted the hand.
In a fifty third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty second aspects, the method further comprising: establishing a measure of a likelihood that the person has an infection, based at least in part on the measure of the concentration of the particles of interest in the negatively sorted stream.
In a fifty fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty third aspects, wherein establishing the measure of the likelihood that the person has an infection comprises: repeatedly passing samples of the fluid obtained at different times through the negative sorting device; for each of the samples of the fluid, analyzing the negatively sorted stream to obtain the measure of the concentration of the particles of interest in the negatively sorted stream; and determining whether the measure of the concentration of the particles of interest in the negatively sorted stream has changed over time.
In a fifty fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty fourth aspects, wherein establishing the measure of the likelihood that the person has an infection comprises comparing the measure of the concentration of the particles of interest in the negatively sorted stream to a comparison measure of the concentration of the particles of interest in the negatively sorted stream.
In a fifty sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty fifth aspects, wherein the comparison measure of the concentration of the particles of interest in the negatively sorted stream comprises a known or estimated measure of the concentration of the particles of interest in the negatively sorted stream when the fluid contains none of the particles of interest.
In a fifty seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty sixth aspects, wherein the comparison measure of the concentration of the particles of interest in the negatively sorted stream comprises a known or estimated measure of the concentration of the particles of interest in the negatively sorted stream when the fluid is prepared under a baseline condition.
In a fifty eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty seventh aspects, wherein the baseline condition comprises an absence of an infection in an individual from which the fluid is obtained.
In a fifty ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty eighth aspects, wherein the comparison measure of the concentration of the particles of interest in the negatively sorted stream comprises a known or estimated measure of the concentration of the particles of interest in the negatively sorted stream when the fluid is prepared under a target condition.
In a sixtieth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to fifty ninth aspects, wherein the target condition comprises a presence of an infection in an individual from which the fluid is obtained.
In a sixty first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixtieth aspects, the method further comprising: performing an action when the measure of the likelihood that the person has an infection is at or above a threshold level.
In a sixty second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty first aspects, the method further comprising: performing an action when the measure of the concentration of the particles of interest in the negatively sorted stream is at least one of: within a target range of values; above a target threshold value; and below a target threshold value.
In a sixty third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty second aspects, wherein performing the action comprises at least one of: providing an alert indicating that the person may have an infection; providing a message to the person indicating that the person should seek medical attention; providing a message to the person indicating that the person should get tested for an infection; and transmitting information to an infection monitoring system.
In a sixty fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty third aspects, wherein performing the action comprises transmitting information to the infection monitoring system; and wherein the information includes a time and a location of the dispensing of the fluid onto the hand.
In a sixty fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty fourth aspects, wherein the information comprises information that identifies the person.
In a sixty sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty fifth aspects, wherein establishing the measure of the likelihood that the person has an infection is also based in part on at least one of: a biological function or characteristic of the person; a temperature of the person; a location of the person; a reported or detected symptom of the person; a blood-oxygen concentration of the person; a travel history of the person; and a behavior of the person.
In a sixty seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty sixth aspects, the method further comprising: collecting data about the person from a mobile device carried by the person.
In a sixty eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty seventh aspects, wherein the mobile device comprises at least one of: a smartphone; a smartwatch; a biosensor; and an activity tracker.
In a sixty ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty eighth aspects, wherein the fluid is dispensed from a hand cleaning fluid dispenser, the hand cleaning fluid dispenser including the negative sorting device and an analyzing device that performs the analysis of the negatively sorted stream to obtain the measure of the concentration of the particles of interest in the negatively sorted stream; the method further comprising compiling data from the hand cleaning fluid dispenser and a plurality of additional hand cleaning fluid dispensers, each of the plurality of additional hand cleaning fluid dispensers including a respective said negative sorting device and a respective said analyzing device.
In a seventieth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to sixty ninth aspects, the method further comprising: estimating a prevalence of an infectious disease in a group of human beings based at least in part on data from the analyzing devices of the hand cleaning fluid dispenser and the plurality of additional hand cleaning fluid dispensers.
In a seventy first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventieth aspects, wherein the plurality of additional hand cleaning fluid dispensers are located at a variety of different geographic locations; and wherein estimating the prevalence of the infectious disease in the group of human beings comprises estimating the prevalence of the infectious disease at each of the different geographic locations over time.
In a seventy second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy first aspects, the method further comprising performing an operation when the prevalence of the infectious disease is estimated to be above a threshold quantity at one of the different geographic locations.
In a seventy third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy second aspects, wherein the operation comprises at least one of: providing a warning about the estimated prevalence of the infectious disease at the one of the different geographic locations; providing a warning to avoid the one of the different geographic locations; providing a warning that those in the one of the different geographic locations may be at increased risk of infection; providing a message that those in the one of the different geographic locations should get tested for the infectious disease; and providing a message that those in the one of the different geographic locations should adopt behavior that reduces a risk of transmitting the infectious disease.
In a seventy fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy third aspects, wherein the particles of interest are primary particles of interest, the method further comprising analyzing the at least one focused fluid stream to determine whether the at least one focused fluid stream contains a threshold amount of secondary particles of interest.
In a seventy fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy sixth aspects, wherein the secondary particles of interest comprise a biological particle.
In a seventy sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy fifth aspects, wherein the secondary particles of interest comprise a bacterial particle.
In a seventy seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy sixth aspects, wherein the primary particles of interest comprise viral particles.
In a seventy eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy seventh aspects, the method further comprising: filtering the fluid before the fluid is passed through the negative sorting device.
In a seventy ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to seventy eighth aspects, wherein filtering the fluid comprises removing any particles from the fluid that are above a secondary threshold size; and wherein the secondary threshold size is larger than the threshold size.
In an eightieth aspect, the present invention resides in a fluid dispenser, which optionally incorporates one or more features of one or more of the first to seventy ninth aspects, the fluid dispenser comprising: a fluid pump that dispenses a fluid onto a user's hand when activated; a collection device that collects the fluid after the fluid has contacted the user's hand; a negative sorting device that receives the fluid from the collection device and produces a negatively sorted stream of the fluid from which particles present in the fluid that are above a threshold size have been removed; and an analyzing device that analyzes the negatively sorted stream to obtain a measure of a concentration of particles of interest in the negatively sorted stream; wherein the particles of interest have a size that is less than or equal to the threshold size.
In an eighty first aspect, the present invention resides in use of the fluid dispenser in accordance with the eightieth aspect for performing the method in accordance with any one or more of the first to seventy ninth aspects.
In an eighty second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty first aspects, the method comprising: providing a fluid that is less polar than pure water; and analyzing the fluid to obtain a measure of a concentration of particles of interest in the fluid; wherein analyzing the fluid comprises measuring an electrical impedance of the fluid.
In an eighty third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty second aspects, wherein the fluid comprises alcohol.
In an eighty fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty third aspects, wherein the fluid comprises water.
In an eighty fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty fourth aspects, wherein the fluid comprises isopropanol, ethanol, or a combination of isopropanol and ethanol.
In an eighty sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty fifth aspects, wherein the electrical impedance of the fluid decreases as the concentration of the particles of interest increases.
In an eighty seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty sixth aspects, wherein the particles of interest comprise at least one of: a biological particle, a bacterial particle, a viral particle, and an infectious agent.
In an eighty eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty seventh aspects, the method further comprising passing the fluid through a microfluidic particle sorter that sorts at least some particles present in the fluid by size and/or shape.
In an eighty ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty eighth aspects, the method comprising: passing a fluid through a microfluidic particle sorter that sorts at least some particles by size; and analyzing at least one fluid stream produced by the microfluidic particle sorter to obtain a measure of a concentration of particles of interest in the at least one fluid stream.
In a ninetieth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to eighty ninth aspects, the method further comprising: dispensing the fluid onto a hand of a person; collecting the fluid after the fluid has contacted the hand; and directing the fluid to the microfluidic particle sorter after the fluid has contacted the hand.
In a ninety first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninetieth aspects, the method further comprising: establishing a measure of a likelihood that the person has an infection, based at least in part on the measure of the concentration of the particles of interest in the at least one fluid stream.
In a ninety second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety first aspects, wherein the fluid is dispensed from a hand cleaning fluid dispenser, the hand cleaning fluid dispenser including the microfluidic particle sorter and an analyzing device that performs the analysis of the at least one fluid stream to obtain the measure of the concentration of the particles of interest in the at least one fluid stream; the method further comprising compiling data from the hand cleaning fluid dispenser and a plurality of additional hand cleaning fluid dispensers, each of the plurality of additional hand cleaning fluid dispensers including a respective said microfluidic particle sorter and a respective said analyzing device.
In a ninety third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety second aspects, the method further comprising: estimating a prevalence of an infectious disease in a group of human beings based at least in part on data from the analyzing devices of the hand cleaning fluid dispenser and the plurality of additional hand cleaning fluid dispensers.
In a ninety fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety third aspects, wherein the particles of interest comprise at least one of: a biological particle, a bacterial particle, a viral particle, and an infectious agent.
In a ninety fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety fourth aspects, wherein the at least one fluid stream comprises a first fluid stream; wherein the microfluidic particle sorter focuses the particles of interest into the first fluid stream; wherein the particles of interest comprise a bacterial particle; wherein the microfluidic particle sorter produces a second fluid stream from which particles present in the fluid that are above a threshold size have been removed; the method further comprising: analyzing the second fluid stream to obtain a measure of a concentration of secondary particles of interest in the second fluid stream; wherein the particles of interest have a size that is greater than the threshold size; wherein the secondary particles of interest have a size that is less than or equal to the threshold size; and wherein the secondary particles of interest comprise a viral particle.
In a ninety sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety fifth aspects, the method comprising: passing a fluid through a negative sorting device that produces a negatively sorted stream of the fluid from which particles present in the fluid that are above a threshold size have been removed; and analyzing the negatively sorted stream to obtain a measure of a concentration of particles of interest in the negatively sorted stream; wherein the particles of interest have a size that is less than or equal to the threshold size.
In a ninety seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety sixth aspects, wherein the negative sorting device comprises a microfluidic particle sorter that produces at least one focused fluid stream and at least one unfocused fluid stream; wherein the microfluidic particle sorter directs the particles present in the fluid that are above the threshold size into the at least one focused fluid stream; and wherein the at least one unfocused fluid stream comprises the negatively sorted stream.
In a ninety eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety seventh aspects, wherein the particles of interest comprise at least one of: a biological particle; a bacterial particle; a viral particle; and an infectious agent.
In a ninety ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety eighth aspects, wherein analyzing the negatively sorted stream comprises measuring an electrical impedance of the negatively sorted stream.
In a one hundredth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to ninety ninth aspects, wherein analyzing the negatively sorted stream comprises comparing the electrical impedance of the negatively sorted stream to a comparison electrical impedance value.
In a one hundred and first aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundredth aspects, wherein the comparison electrical impedance value comprises a known or estimated electrical impedance of the fluid when the fluid contains none of the particles of interest.
In a one hundred and second aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and first aspects; wherein the comparison electrical impedance value comprises a known or estimated electrical impedance of the fluid when the fluid contains a baseline concentration of the particles of interest; wherein the baseline concentration of the particles of interest comprises a known or estimated concentration of the particles of interest in the fluid when the fluid is prepared under a baseline condition; and wherein the baseline condition comprises an absence of an infection in an individual from which the fluid is obtained.
In a one hundred and third aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and second aspects, wherein the comparison electrical impedance value comprises a known or estimated electrical impedance of the fluid when the fluid contains a target concentration of the particles of interest; wherein the target concentration of the particles of interest comprises a known or estimated concentration of the particles of interest in the fluid when the fluid is prepared under a target condition; and wherein the target condition comprises a presence of an infection in an individual from which the fluid is obtained.
In a one hundred and fourth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and third aspects, wherein the fluid comprises at least one of: an alcohol; and a hand cleaning fluid.
In a one hundred and fifth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and fourth aspects, further comprising at least one of: collecting the fluid from a body of a human or an animal; and placing a sample in the fluid, the sample containing particles collected from an object, an organism, or an environment.
In a one hundred and sixth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and fifth aspects, further comprising: contacting the fluid with a surface; and directing the fluid to the negative sorting device after the fluid has contacted the surface.
In a one hundred and seventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and sixth aspects, wherein the surface comprises an internal surface or an external surface of a human body.
In a one hundred and eighth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and seventh aspects, wherein analyzing the negatively sorted stream comprises optically detecting particles in the negatively sorted stream.
In a one hundred and ninth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and eighth aspects, wherein analyzing the negatively sorted stream comprises: obtaining an optical image of the fluid in the negatively sorted stream; and analyzing the optical image to count, calculate, or estimate a quantity of the particles of interest in the optical image.
In a one hundred and tenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and ninth aspects, further comprising: dispensing the fluid onto a hand of a person; collecting the fluid after the fluid has contacted the hand; and directing the fluid to the negative sorting device after the fluid has contacted the hand.
In a one hundred and eleventh aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and tenth aspects, wherein analyzing the negatively sorted stream comprises measuring an electrical impedance of the negatively sorted stream; wherein analyzing the negatively sorted stream comprises comparing the electrical impedance of the negatively sorted stream to a comparison electrical impedance value; wherein the comparison electrical impedance value comprises at least one of: (i) a known or estimated electrical impedance of the fluid when the fluid contains none of the particles of interest; (ii) a known or estimated electrical impedance of the fluid when the fluid contains a baseline concentration of the particles of interest; wherein the baseline concentration of the particles of interest comprises a known or estimated concentration of the particles of interest in the fluid when the fluid is prepared under a baseline condition; and wherein the baseline condition comprises an absence of an infection in an individual from which the fluid is obtained; and (iii) a known or estimated electrical impedance of the fluid when the fluid contains a target concentration of the particles of interest; wherein the target concentration of the particles of interest comprises a known or estimated concentration of the particles of interest in the fluid when the fluid is prepared under a target condition; and wherein the target condition comprises a presence of an infection in an individual from which the fluid is obtained.
In a one hundred and twelfth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and eleventh aspects, wherein the fluid comprises at least one of: an alcohol; and a hand cleaning fluid.
In a one hundred and thirteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and twelfth aspects, further comprising at least one of: (i) collecting the fluid from a body of a human or an animal; (ii) placing a sample in the fluid, the sample containing particles collected from an object, an organism, or an environment; and (iii) contacting the fluid with a surface, and directing the fluid to the negative sorting device after the fluid has contacted the surface, wherein the surface comprises an internal surface or an external surface of a human body.
In a one hundred and fourteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and thirteenth aspects, wherein analyzing the negatively sorted stream comprises optically detecting particles in the negatively sorted stream; and wherein analyzing the negatively sorted stream comprises: obtaining an optical image of the fluid in the negatively sorted stream; and analyzing the optical image to count, calculate, or estimate a quantity of the particles of interest in the optical image.
In a one hundred and fifteenth aspect, the present invention resides in a method, which optionally incorporates one or more features of one or more of the first to one hundred and fourteenth aspects, further comprising: dispensing the fluid onto a hand of a person; collecting the fluid after the fluid has contacted the hand; and directing the fluid to the negative sorting device after the fluid has contacted the hand.
Further aspects and advantages of the invention will appear from the following description taken together with the accompanying drawings, in which:
Referring to
The housing 12 has a back plate 30, spaced side walls 32 and 34, and a top wall 36 defining an interior cavity 38 therebetween. The fluid reservoir 14 is a plastic bottle that sits within the interior cavity 38 of the housing 12 and contains a supply of the hand cleaning fluid 22 to be dispensed from the dispenser 10. The hand cleaning fluid 22 may, for example, be hand sanitizer containing an alcohol such as isopropanol and/or ethanol. The reservoir 14 may have any suitable structure, such as that shown and described in U.S. Pat. No. 7,748,573 to Anhuf et al., and is removable from the housing 12 so that it can be refilled or replaced when the supply of fluid 22 within the reservoir 14 is running low, as is described and shown in more detail in U.S. Pat. No. 7,748,573 to Anhuf et al.
The pump mechanism 16 is coupled to the fluid reservoir 14 for dispensing the fluid 22 contained in the fluid reservoir 14 out through the fluid outlet 24. The pump mechanism 16 may have any suitable structure, and may for example be in the form of a piston pump assembly as shown and described in U.S. Pat. No. 7,748,573 to Anhuf et al. The pump mechanism 16 is activated by depressing the actuator lever 18 from the rest position of
The nozzle shield 20 is removably coupled to the housing 12 and has a similar structure to that shown and described in U.S. Pat. No. 7,748,573 to Anhuf et al. When coupled to the housing 12, the nozzle shield 20 substantially covers the pump mechanism 16, protecting the pump mechanism 16 from contamination and damage. As can be seen in
As shown in
The fluid receiving platform 50 has a plurality of small drainage holes 52 that extend vertically through the fluid receiving platform 50. As shown in
The fluid 22 that is received by the fluid receiving channel 60 is directed through a fluid pathway 62. As shown schematically in
The filter 64 is preferably configured to remove any large particles that may be present in the fluid 22, such as large particles of dirt or clusters of dead skin. The filter 64 may, for example, be configured to remove any particles larger than 60 microns.
The fluid pump 66 is configured to pump the fluid 22 through the fluid pathway 62 from the inlet opening 58 to the waste storage chamber 70. Any suitable fluid pump 66 construction could be used, including for example a pump 66 driven by an electric motor. The fluid pump 66 is configured to pass the fluid 22 through the microfluidic particle sorter 68 with sufficient fluid pressure and/or flow velocity to achieve the desired particle sorting, as described in more detail below.
The microfluidic particle sorter 68 is shown schematically in
As shown schematically in
The first output channel 82 extends from the branch point 80 to a first channel outlet 88, and the second output channel 84 extends from the branch point 80 to a second channel outlet 90. The fluid 22 that has passed through the microfluidic particle sorter 68 is discharged from the first channel outlet 88 and the second channel outlet 90 into the waste storage chamber 70. As shown in
As shown schematically in
A first preferred manner of operating the fluid dispenser 10 will now be described with reference to
The fluid 22 that drips into the drip tray 40 from the user's hand 28 passes through the drainage holes 52 and into the fluid collecting chamber 54, where it is directed to the inlet opening 58 by the fluid collecting surface 56. The fluid 22 is then drawn through the fluid pathway 62 by the fluid pump 66. As the fluid 22 passes through the filter 64, large particles such as clusters of dead skin are removed from the fluid 22. The filtered fluid 22 then passes through the fluid pump 66 and into the microfluidic particle sorter 68.
The fluid 22 enters the microfluidic particle sorter 68 at the microchannel inlet 76, and travels through the spiral shaped sorting microchannel 78 towards the branch point 80 under the fluid pressure generated by the fluid pump 66. As the fluid 22 travels through the sorting microchannel 78, at least some of the particles present in the fluid 22 are sorted by size and/or shape.
The particles that are sorted by the sorting microchannel 78 depend on the operating parameters of the microfluidic particle sorter 68, including the microchannel structure 74, the fluid pressure, and the type of fluid 22 in which the particles are carried. For example, as can be seen in the enlarged view of the branch point 80 shown in
In the embodiment shown in
The measure of the concentration of viruses 102 obtained by the first analyzing device 86 is transmitted to the processor 96, which is preferably configured to establish a measure of the likelihood that the user 26 has an infection based at least in part on the measure of the concentration of viruses 102 in the fluid 22. The processor 96 may, for example, compare the measure of the concentration of viruses 102 in the fluid 22 to a baseline value. The baseline value may, for example, be the expected or measured electrical impedance of the fluid 22 when the fluid 22 contains no viruses 102.
Depending on the properties of the fluid 22 and the particle of interest, the electrical impedance of the fluid 22 will preferably vary in a predictable manner depending on the concentration of the particles of interest in the fluid 22. For example, if the fluid 22 has a high concentration of alcohol, such as ethanol or isopropanol, the electrical impedance of the fluid 22 would generally be expected to decrease as the concentration of viruses 102 in the fluid 22 increases. The relationship between electrical impedance and the concentration of particles of interest for different combinations of fluids 22 and particles of interest can be determined by routine experimentation.
Optionally, if the processor 96 determines that there is any measurable increase in the concentration of particles in the negatively sorted stream 104 as compared to the baseline, then the processor 96 may be configured to conclude that the user 26 likely has an infection. Alternatively, the difference between the measure of the concentration of the particles of interest in the fluid 22 and the baseline value may need to exceed a threshold quantity before the processor 96 determines that the user 26 likely has an infection. The threshold quantity may be selected, for example, to reduce the likelihood of false positives as a result of minor variations in the electrical impedance of the fluid 22 that are caused by factors other than the concentration of viruses 102. For example, in some embodiments of the invention the electrical impedance of the fluid 22 may vary slightly in comparison to a baseline value due to the loss of alcohol by evaporation.
If the processor 96 determines that the user 26 likely has an infection, the processor 96 may for example cause the indicator light 42 to flash red. This is preferably understood by the user 26 as indicating a possible infection, so that the user 26 can take appropriate action such as self-isolating or obtaining a test for a specific pathogen of concern, such as COVID-19. There may, for example, be a sign placed beside the dispenser 10 that advises users 26 what to do in the event that the indicator light 42 flashes red. If the processor 96 determines that there is no sign of an infection, the processor 96 may for example cause the indicator light 42 to light up green.
The processor 96 may also be configured to communicate with external devices via the communication device 98. The processor 96 may, for example, use the communication device 98 to wirelessly send a signal to an external infection monitoring system when a possible infection is detected. The infection monitoring system may, for example, be used by public health authorities to track the prevalence of infections in different geographic locations based at least in part on data received from a plurality of the fluid dispensers 10 installed in different locations.
Optionally, the processor 96 is configured to use the communication device 98 to communicate directly with a mobile device carried by the user 26, such as a smartwatch or smartphone. The processor 96 may, for example, cause the mobile device to display a warning to the user 26 if the processor 96 determines that the user 26 may have an infection. The processor 96 may also receive information from the mobile device via the communication device 98, such as information about the identity of the user 26, the travel history of the user 26, and biological information such as heartrate, blood pressure, respiratory function, and blood-oxygen concentration. Some or all of this information may then be transmitted by the communication device 98 to the infection monitoring system.
The processor 96 may also use additional data when establishing a measure of the likelihood that the user 26 has an infection. For example, the fluid dispenser 10 optionally includes an infrared temperature sensor 150, shown in dotted lines in
Optionally, the dispenser 10 is configured to analyze the fluid 22 in the second output channel 84 in addition to or in place of the analysis of the fluid 22 in the first output channel 82. The microfluidic particle sorter 68 may, for example, include a second analyzing device 106, as shown schematically in dotted lines in
Optionally, the processor 96 is configured to establish a measure of the likelihood that the user 26 has a bacterial infection based at least in part on the measure of the concentration of bacteria 100 in the second output channel 84 obtained by the second analyzing device 86. The processor 96 may, for example, compare the measure of the concentration of bacteria 100 in the second output channel 84 to a baseline value. The baseline value may, for example, be the measure of the concentration of bacteria 100 in fluid 22 obtained from a person who is known to not have a bacterial infection. Optionally, if the measure of the concentration of bacteria 100 in the second output channel 84 exceeds the baseline value by a threshold quantity, then the processor 96 may determine that the user 26 has a possible bacterial infection. This determination may be indicated to the user 26 by, for example, illuminating the indicator light 42 in flashing red light.
As the second output channel 84 may also include particles present in the fluid 22 that were unfocused or unsorted by the microfluidic particle sorter 68, such as viruses 102, in some embodiments of the invention the measure of the concentration of the second particles of interest may be adjusted or processed to account for the possible presence of unfocused or unsorted particles in the second output channel 84. For example, the processor 96 may be configured to adjust the measure of the concentration of the second particles of interest based on the measure of the concentration of the primary particles of interest in the first output channel 82 obtained by the first analyzing device 86. In embodiments where the first and second analyzing devices 86 and 106 measure the electrical impedance of the fluid 22 in the first and second output channels 82 and 84, respectively, the electrical impedance value of the fluid 22 in the first output channel 82 may for example be used as a baseline value against which the electrical impedance of the fluid 22 in the second output channel 84 is compared. For example, if the electrical impedance of the fluid 22 in the second output channel 84 is the same as the electrical impedance of the fluid 22 in the first output channel 84, this may be used as an indication that the second output channel 84 contains no measurable quantity of the second particle of interest. If the electrical impedance of the fluid 22 in the second output channel 84 is lower than the electrical impedance of the fluid 22 in the first output channel 84, this may be used as an indication that the second output channel 84 does appear to contain a measurable quantity of the second particle of interest. The magnitude of the difference between the electrical impedance of the fluid 22 in the first output channel 82 and the electrical impedance of the fluid 22 in the second output channel 84 may be used to obtain a measure of the concentration of the second particle of interest in the second output channel 84 that is adjusted for the possible presence of unfocused or unsorted particles in the second output channel 84.
Reference is now made to
The first stage microfluidic particle sorter 108 shown in
The first stage microfluidic particle sorter 108 has a microchannel structure 74 including a microchannel inlet 76 that receives the fluid 22 from the fluid pump 66 and a spiral shaped sorting microchannel 78 that extends from the microchannel inlet 76 to a branch point 80 where the sorting microchannel 78 splits into a first stage unfocused output channel 110 and a first stage focused output channel 112. The operating parameters of the first stage microfluidic particle sorter 108 may for example be selected so that relatively large particles, such as skin cells 114, are focused and directed into the first stage focused output channel 112, as shown in
The fluid 22 in the first stage unfocused output channel 110 is preferably directed into the microchannel inlet 76 of the second stage microfluidic particle sorter 68 for further processing and analysis. The second stage microfluidic particle sorter 68 focuses the bacteria 100 into the second output channel 84 and leaves the viruses 102 unfocused and present in both the first output channel 82 and the second output channel 84, as described above with respect to the first embodiment of the invention and shown in
Optionally, the first stage microfluidic particle sorter 108 could include a third analyzing device 116, shown schematically in dotted lines in
Reference is now made to
The microfluidic particle sorter 68 shown in
The operating parameters of the microfluidic particle sorter 68 shown in
Reference is now made to
The microfluidic particle sorter 68 partially shown in
The microfluidic particle sorter 68 partially shown in
Reference is now made to
The microfluidic particle sorter 68 shown in
In the embodiment shown in
In the embodiment shown in
Reference is now made to
As shown in
The microfluidic particle sorter 68 used in the experiment is the Fluidic 382™ microfluidic spiral sorter manufactured by microfluidic ChipShop GmbH. The Fluidic 382™ microfluidic spiral sorter has four different microchannel structures 74 formed in the chip body 72. For the experiment, the second microchannel structure 74 was used, labelled with the numeral 74 in
To perform the experiment, the syringe 122 was filled with water containing E. coli bacteria 100, 3 micron beads 132, 5 micron beads 134, and 10 micron beads 136. The syringe pump 120 was used to pump the water (ultrapure water, 18.2 MOhms·cm resistivity) from the syringe 122, through the tube 124, and through the microfluidic particle sorter 68 at a flow velocity of 550 mL/min. The microscope 126 was used to obtain microscopic images of the distribution of the E. coli bacteria 100, the 3 micron beads 132, the 5 micron beads 134, and the 10 micron beads 136 in the sorting microchannel 78 of the microfluidic particle sorter 68.
As can be best seen in
The experimental setup therefore produced a negatively sorted stream 104 that contained some of the particles that were 3 microns or less, and from which the particles larger than 3 microns were removed. If the operational parameters of the microfluidic particle sorter 68 were adjusted, including for example the geometry of the sorting microchannel 78 and/or the flow velocity, the size of the particles that are focused or sorted by the microfluidic particle sorter 68 could be adjusted. For example, it would be possible to adjust the operational parameters so that the 3 micron beads 132 are focused or sorted, and/or the E. coli bacteria 100, which have a width of about 1 micron, are focused or sorted. Generally, smaller canals and higher flow velocities would be needed to focus smaller particles.
Reference is now made to
The unfocused stream of fluid 22 in the middle canal of the first stage sorter 144 is directed into the microchannel inlet 76 of the second stage sorter 146 shown in
An unfocused stream of fluid 22 containing unfocused or unsorted particles such as individual bacteria cells 100 and viruses 102 is outputted by the second stage sorter 146 into the microchannel inlet 76 of the third stage sorter 148 shown in
Reference is now made to
The fluid dispenser 10 shown in
Reference is now made to
Reference is now made to
Reference is now made to
Reference is now made to
Viruses 102 can be detected by the negative sorting and are generally only present when a viral infection is present. In other words, the detection of viruses 102 is preferably a 100% positive detection of a viral infection. If a bacterial infection is present one of the branches may show an increased concentration of particles compared to a baseline. The branch with the increased concentration may provide evidence of a specific infection. The method is preferably able to narrow the type of bacterial infection down to a few different candidates, based for example on the size and/or shape of the bacteria 100 and/or cluster type. Even spores of a Bacillus and Clostridium could preferably be detected as spores will preferably be sorted as separated particles in one particular canal.
Reference is now made to
Reference is now made to
The fluid dispenser 10 shown in
It will be understood that, although various features of the invention have been described with respect to one or another of the embodiments of the invention, the various features and embodiments of the invention may be combined or used in conjunction with other features and embodiments of the invention as described and illustrated herein.
The invention is not limited to the particular construction of the fluid dispenser 10, including the actuator lever 18, the fluid outlet 24, the housing 12, the fluid reservoir 14, the pump mechanism 16, the drip tray 40, or the nozzle shield 20, as shown in the drawings. Rather, any fluid dispenser 10 construction could be adapted to perform the method of the present invention, including for example those taught in U.S. Pat. No. 8,245,877 to Ophardt, issued Aug. 21, 2012; U.S. Pat. No. 8,113,388 to Ophardt et al., issued Feb. 14, 2012; U.S. Pat. No. 8,091,739 to Ophardt et al., issued Jan. 10, 2012; U.S. Pat. No. 7,748,573 to Anhuf et al., issued Jul. 6, 2010; U.S. Pat. No. 7,984,825 to Ophardt et al., issued Jul. 26, 2011; U.S. Pat. No. 8,684,236 to Ophardt, issued Apr. 1, 2014; U.S. Pat. No. 5,373,970 to Ophardt, issued Dec. 20, 1994; U.S. Pat. No. 5,836,482 to Ophardt et al., issued Nov. 17, 1998; and U.S. Pat. No. 9,682,390 to Ophardt et al., issued Jun. 20, 2017, which are each incorporated herein by reference. Although the fluid dispenser 10 shown in
Optionally, the fluid dispenser 10 has an infection testing mode in which a greater quantity of fluid 22 is dispensed than when in a hand sanitizing mode, so that sufficient overspray is produced so that the fluid 22 drips off of the user's hand 28 and into the drip tray 40. The fluid dispenser 10 could also optionally be configured to dispense a different fluid 22 when in the infection testing mode than when in the hand sanitizing mode.
The invention is not limited to being performed by or using a hand cleaning fluid dispenser 10. Rather, the method could for example be performed as a standalone method for testing for a pathogen, such as a virus 102. For example, the fluid 22 could be swished around a person's mouth before being processed and analyzed in accordance with the invention, to for example test for the presence of viruses 102. The fluid 22 could, for example, be water. Any suitable method of obtaining a sample fluid 22 could be used, including for example swabbing a part of the user's body such as their nose, face, ears, tongue, or hands, and then placing the swab in the fluid 22 to disburse particles present on the swab into the fluid 22. Other non-biological surfaces could be swabbed as well, such as for example, door knobs, desks, railings, or chairs, to for example test for the presence of viruses 102 in a particular room, environment, workplace, or group of persons. Optionally, the method could be adapted to test for airborne particles by, for example, passing an air sample from a ventilation system through a fluid 22 so that particles present in the air become dispersed in the fluid 22, and then processing and analyzing the fluid 22 in accordance with the invention. The invention may also be used for example to test for contaminants on products, such as food products, by for example running fluid 22 over the food products and then processing and analyzing the fluid 22 in accordance with the invention.
The invention is not limited to any particular set of operational parameters for the microfluidic particle sorter 68, including for example the type of fluid 22; the size and shape of the sorting microchannel 78; the number of output channels 82, 84, 118; the particle sizes and/or shapes that are sorted and/or negatively sorted; and the flow velocity and/or fluid pressure. The operating parameters may be adapted as necessary to provide the desired sorting and/or negative sorting. The operating parameters that allow for sorting and/or negative sorting of a particular particle of interest or a particular size and/or shape of particle may be determined through routine experimentation. In order to negatively sort a particular particle of interest, the operating parameters should be selected so that particles above a threshold size are focused and separated into one or more distinct channels or streams, the threshold size being larger than the size of the particle of interest. Optionally, the invention may be performed using a single microfluidic particle sorter 68 having any suitable number of output channels 82, 84, 118, or with an array of multiple microfluidic particle sorters 68. When an array of multiple microfluidic particle sorters 68 is used, the output from one or more output channels 82, 84, 118 may be used as the input for a subsequent microfluidic particle sorter 68 in the array. The microfluidic particle sorter 68 is also referred to herein as the negative sorting device 68.
Any suitable shape of the sorting microchannel 78 could be selected that provides the desired sorting and/or negative sorting of particles, including for example any one or more of the following: curved segments, straight segments, spiral segments, serpentine segments, and segments where the width and/or depth of the microchannel 78 changes.
The microfluidic particle sorter 68 could be made from any suitable material or materials, including one or more of the following: polymers, silicon, metal, and glass.
The invention may use any suitable apparatus, method, and/or technique for analyzing the fluid 22. The fluid 22 in every output channel 82, 84, 118 or in only selected output channels 82, 84, 118 may be analyzed to obtain a measure of the concentration of particles in the fluid 22. Optionally, the analysis of the fluid 22 in each of the different output channels 82, 84, 118 may be performed using the same apparatus, method, and/or technique, or the analysis of the fluid 22 in some output channels 82, 84, 118 may be performed using a different apparatus, method, and/or technique.
In some embodiments of the invention, the fluid 22 in the negatively sorted stream 104 and/or the focused stream or streams may be analyzed optically to detect particles in the fluid 22. For example, a microscope 126 could be incorporated into the fluid dispenser 10 in the manner as shown in
In at least some preferred embodiments of the invention, the analysis of the fluid 22 can be imperfect, and does not need to provide conclusive proof of the exact concentration of a particular particle of interest, such as a virus 102, in the fluid 22. Rather, the analysis is preferably cheap, low cost, and fast, and provides an indication of a possible infection, which can then be investigated further. For example, if the measure of the concentration of particles in a particular sorted and/or negatively sorted stream of fluid 22 is higher than normal, this can be used as an indication of a possible infection, which can then be investigated further using for example a culture test or a PCR test for a particular pathogen or pathogens of concern. Likewise, an increase in the prevalence of higher than normal concentrations of particles of particular sizes in a particular geographic location as measured by multiple fluid dispensers 10 may provide an indication that something unusual is occurring at that geographic location that should be investigated further.
In some embodiments of the invention, the measure of the particles of interest that is obtained does not necessarily provide conclusive proof that the particles of interest are present in the fluid 22, or that the particles of interest are present at a particular concentration or range of concentrations. For example, depending on how the measure of the concentration of the particles of interest is obtained, the measure could be affected by the presence of other particles in the fluid 22 that are not the particles of interest. In some embodiments of the invention, the presence of very small dirt particles in the fluid 22 may, for example, impact the measure of the concentration of the particles of interest that is obtained. Any analysis that provides a result, measurement, or value that would in at least some circumstances be dependent on the concentration of the particles of interest in the fluid 22 could be considered to be providing a measure of the concentration of the particles of interest in the context of the present invention, even if the result, measurement, or value does not provide conclusive proof of the actual presence or concentration of the particles of interest.
The invention is not limited to the use of any particular fluid 22. Rather, any suitable fluid 22 for performing the desired processing and analysis could be used. For example, in at least some embodiments of the invention the fluid 22 could include one or more of: water, a buffered polar solution, acids, bases, ionic fluids, alcohol, water mixed with alcohol, water mixed with at least 30% alcohol, water mixed with at least 50% alcohol, water mixed with at least 60% alcohol, water mixed with at least 70% alcohol, water mixed with at least 80% alcohol, water mixed with at least 90% alcohol, water mixed with at least 95% alcohol, pure alcohol, isopropanol, ethanol, methanol, a polar liquid or solution, or a non-polar liquid or solution, independent of its pH or any other additives. In some embodiments of the invention, the fluid 22 may comprise a bodily fluid such as saliva, tears, sweat, mucous, or urine.
In some preferred embodiments of the invention, the fluid 22 is selected to be non-polar or to have a low polarity, as compared for example with pure water. The fluid 22 may for example include an alcohol such as isopropanol mixed with water. The applicant has found that fluids 22 that are non-polar or have a low polarity, including concentrated isopropanol, have a relatively high electrical impedance when no particles are present in the fluid 22. When biological particles such as viruses 102 or bacteria 100 are present in the fluid 22, for example in the case of isopropanol, the electrical impedance decreases. As dirt particles are generally electrical insulators, any dirt particles that may be present in the fluid 22 would not be expected to decrease the electrical impedance of the fluid 22. As such, when electrical impedance is used as a measure of the concentration of biological particles such as viruses 102 or bacteria 100 in a non-polar or low polarity fluid 22, the presence of dirt particles in the fluid 22 preferably does not substantially affect the electrical impedance measurement. This preferably improves the accuracy of the measure of the concentration of the particles of interest in the fluid 22. For example, if the fluid 22 is non-polar or has a low polarity, a decrease in the electrical impedance of the fluid 22 preferably provides a relatively reliable indication that biological particles of interest are present in the fluid 22, rather than an insulating particle such as dirt. In contrast, if a polar fluid 22 such as water is used, the presence of insulating particles such as dirt in the fluid 22 would be expected to affect the electrical impedance of the fluid 22, which could cause the electrical impedance to be a less accurate measure of the concentration of the particles of interest in the fluid 22.
Any suitable manner of directing the fluid 22 through the microfluidic particle sorter 68 could be used. Preferably, the operating parameters of the microfluidic particle sorter 68 are selected so that a small, low-powered fluid pump 66 is able to provide the required fluid pressure and/or flow velocity. In some embodiments of the invention, forces such as gravity or capillary forces may be sufficient to produce adequate sorting, without the need for a fluid pump 66.
The invention could also use different methods, techniques, or apparatuses for sorting and/or negative sorting particles in addition to or in place of the microfluidic particle sorter 68. For example, some embodiments of the invention may use other mechanical, magnetic, electrical, and/or optical methods of sorting particles according to size, shape, and/or other characteristics of the particles.
Information about the concentration of particles in the fluid 22 may be used for any desired purpose, and is not limited to the identification of possible infections as described in the preferred embodiments. The invention is not limited to analyzing the concentrations of biological particles, and could be used to detect non-biological particles as well.
In some of the preferred embodiments of the invention described above, the measure of the likelihood that the user 26 has an infection has been described as optionally being informed by a comparison of the measure of the concentration of the particles of interest to a baseline value. The invention is not limited to this manner of establishing the measure of the likelihood that the user 26 has an infection. Rather, any suitable method of estimating or calculating or predicting the likelihood of the presence of an infection could be used. For example, in some embodiments of the invention the measure of the concentration of the particles of interest in the fluid 22 could be tracked over time, using for example samples of the fluid 22 obtained from different users 26 of the fluid dispenser 10 over time. Changes in the measure of the concentration of the particles of interest over time could then be monitored and used to inform the measure of the likelihood that an infection is present. For example, if the measure of the concentration of the particles of interest is increasing over time, this could be used as an indication that more recent users 26 of the dispenser 10 are more likely to have an infection than were the previous users 26 of the dispenser 10.
The present invention may be used to obtain a measure of the concentration of any suitable particle of interest in a fluid 22, and is not limited to the particular particles identified in the preferred embodiments. For example, the particles of interest could include one or more of the following: viral particles, bacterial particles, prions, parasites, pathogens, spores, fungal particles, proteins, cancer cells, blood cells, human cells, animal cells, enzymes, microplastics, and dust particles. As used herein, the term “viral particles” includes live viruses, dead viruses, fractions of viruses, and clusters of viruses. The term “bacterial particles” as used herein includes live bacteria, dead bacteria, individual bacteria cells, clusters of bacteria cells, chains of bacteria cells, and fractions of bacteria cells.
The term “fluid” as used herein includes any flowable substance, including liquids, solutions, foams, emulsions, acids, bases, and dispersions.
The term “micron” as used herein refers to a micrometer or μm. The particle sizes provided herein, such as 1 micron, 3 microns, 5 microns, and 10 microns, refer to the diameter of the particle, unless otherwise stated.
Although this disclosure has described and illustrated certain preferred embodiments of the invention, it is to be understood that the invention is not restricted to these particular embodiments. Rather, the invention includes all embodiments which are functional, mechanical, chemical, electrical, or optical equivalents of the specific embodiments and features that have been described and illustrated herein.
This application claims priority to the Sep. 21, 2020 filing date of U.S. Provisional Patent Application Ser. No. 63/080,980, which is incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63080980 | Sep 2020 | US |
