WO2022221770A1

WO2022221770A1 - Exhaled breath and liquid sample analyzer and methods

Info

Publication number: WO2022221770A1
Application number: PCT/US2022/025231
Authority: WO
Inventors: Oshiorenoya AGABI
Original assignee: Koniku Inc.
Priority date: 2021-04-16
Filing date: 2022-04-18
Publication date: 2022-10-20

Abstract

A method of detecting a health or medical condition of a patient includes receiving the patient's exhaled breath in an analyzer, exposing living cells in the analyzer to the breath, and identifying a compound in the breath based on a response from the living cells. Alternatively, the method may include receiving a water sample of the patient's stool and/or urine from water in a bowl of a toilet, with the water sample provided from the bowl to an analyzer associated with the toilet. In another method, the analyzer may operate using a saliva or perspiration sample.

Description

EXHALED BREATH AND LIQUID SAMPLE ANALYZER AND METHODS

BACKGROUND OF THE INVENTION

[0001] Humans having certain diseases exhale particles or airborne compounds indicative of the disease. Some in vivo pathogens excrete marker gases. In other cases, the content of a human breath may be influenced by an imminent or actual disease condition. For example, exhaled metabolites can provide information about the state of metabolic processes in the respiratory tract. Exhalation of ketones can indicate diabetes. Thus, the ability to analyze the exhaled breath of humans presents potential detection of various disease and health conditions. In the past, health or disease conditions have been detected, with varying degrees of success, in a laboratory or clinical setting. However, the ability to conduct such analysis in the home would of course allow much more continuous and widespread use. Accordingly, there is a need for improved systems and methods adapted for home use.

SUMMARY OF THE INVENTION

[0002] The inventors have now developed a system for analyzing exhaled breath suitable for home use. The system is advantageously adapted for use in a bathroom. The system may use living biological cells for the purpose of sensing various molecules. The cells may be reprogrammed and manipulated in a variety of ways through genetic modifications. Neuronal or glial cells and derivatives thereof (e.g., olfactory neurons, astrocytes), embryonic cells and derivatives thereof (e.g., HEK293T cells, HANA3A cells), endothelial cells and derivatives thereof (e.g., A549 cells), or stem cells, may be used. The cells may be any wild type or engineered cells that are capable of expressing an olfactory receptor (OR). The cells may be genetically modified to express accessory proteins to facilitate expression of the OR and visualization of its activation; and/or to express factors that increase cell durability, ability to divide and proliferate, or other characteristics to enhance survival when used in the system described herein. Neuron cells express olfactory receptors (OR) on their surfaces. Each olfactory neuron usually expresses only one OR gene among the hundreds present in the organism’s genome. When a molecule from inhaled air binds to a matching receptor, the event triggers OR activation which results in an increase in cytosolic calcium concentration. This concentration can be measured using a calcium sensitive fluorescent reporter such as GCaMP6f. The binding of a molecule to its receptor induces an increase in the fluorescence emitted by the cells. An optical detector can therefore be used to measure cellular response in a contactless manner. The present system and methods may detect molecules of interest using an optical detector that detects fluorescence.

[0003] Other objects, features and advantages will become apparent from the following detailed description and drawings, which are provided as examples for explanation, and are not intended to be limits on the scope of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0004] In the drawings, the same element number indicates the same element in each of the views.

[0005] Fig. 1 is a schematic diagram of a the present system installed on a wall in a bathroom.

[0006] Fig. 2 is a schematic diagram of a user exhaling onto or into an inlet of the system shown in Fig. 1.

[0007] Fig. 3 is a flow chart of steps of a method which may be performed.

[0008] Fig. 4 is a block diagram of sub-systems or modules.

[0009] Fig. 5 is a schematic diagram of the wall-mounted system shown in Fig. 1.

[0010] Fig. 6 is a schematic interior view of the wall-mounted system shown in Fig. 5.

[0011] Fig. 7 is a view of a toilet with an analyzer attached or built in.

[0012] Fig. 8 is a view of a bathroom sink and an analyzer. DETAILED DESCRIPTION

[0013] As shown in Fig. 1 , the present system or analyzer 14 may be mounted on a wall of a bathroom 12. In one embodiment, the analyzer 14 is electrically linked, via wire or wirelessly to a separate wall-mounted touch pad or finger pad 20, and to a display 18. The display 18 may be contained in or on a bathroom mirror 16. Alternatively, the touch pad 20 and display may be included on the analyzer 14, or they may be omitted. Fig. 2 shows a user 10 exhaling onto the analyzer 14. Exhaled particles 22 are drawn into the analyzer 14.

[0014] As shown in Fig. 4, the analyzer 14 includes a power supply 32 electrically connected to an electronic controller or control board 34. The power supply 32 may be a battery or a source of wall current. The control board 34 includes a processor and memory. The control board 34 is electrically connected to cell life support and operation module 36, which may include a pump, sensors, light detectors, LED’s and others, for example as described in U.S. Patent Application No. 17/571 ,363 filed January 7, 2022, incorporated herein by reference. In the systems described here, however, liquid or air is pumped to or across the membrane, rather than only air. The liquid may contain a sample of urine, stool sample water, saliva, or sweat.

[0015] The analyzer 14 may optionally include a communications sub-system or module 38 electrically connected to the control board 34. If used, the communications sub-system may communicate information about breath analysis to an external device, such as a smart phone, computer, medical database, cloud, etc. The communications sub-system may also receive information, such as information to be presented to the user 10, software updates and/or internal diagnostics.

[0016] Referring to Figs. 4, 5 and 6, the analyzer 14 may include a sensor 40 for detecting the entry or presence of the user 10 in the bathroom 12. The sensor 40 may be a motion detector 46, such as an ultrasonic motion detector, or an optical detector 44, such as a camera or infrared detector. A proximity sensor may also be included to detect when the user is close to the analyzer 14, for switching on analyzer operations. The analyzer 14 may also optionally include a user interface 42, which may include a microphone 56 and a speaker or a smart speaker (e.g., Amazon Echo) 48, a finger pad 52, a keypad 50, and/or a display 58, to allow the user 10 to communicate with the analyzer 14. If used, the sensor(s) and user interface components are electrically connected to the control board 34. Generally, the components shown in Fig. 4 may be included in or on the housing 30 of the analyzer. Alternatively, one or more of these components may be provided as separate components. For example, as shown via the dotted lines in Fig. 5, the display 58, if used, may be included in a bathroom mirror, and the key pad 50 may be provided as a separate wall mounted component, or implemented as a software application in smart phone or a dedicated remote device. As shown in Fig. 1 , the analyzer may be provided with a hemispherical or dish-shaped housing 30 of about 8 to 30 cm in diameter, and be adapted for wall-mounting.

[0017] The control board 34 is also electrically connected to air or breath handling module 43 in the analyzer 14. As shown in Fig. 6, the analyzer 14 has an inlet 60 for receiving the user’s exhaled breath. A screen of filter 62 may cover the inlet 60, depending on the exhaled particles the analyzer 14 is adapted to detect and identify. A duct extends from the inlet 60 to an outlet 68. A fan 66 may be included to help move the user’s exhaled breath to the cell assembly 64 and through the housing 30. The cell assembly 64 contains living cells in an array or membrane cartridge, within the cell life support and operations module 36.

[0018] The breath handling module 43 may include an exhalation sensor which senses the user’s exhalation, such as a vane, deflecting plate, hot or cold wire, MEMS. In this case the proximity sensor may be omitted. In some embodiments, no air handling components are used or needed, as the user’s exhale force alone carries the user’s breath sufficiently into the analyzer 14. As shown in Fig. 5, LED’s 54 may be provided on the housing 30 as status or message indicators.

[0019] Turning to Fig. 3, the analyzer may perform methods which include the step of initially detecting the entrance or presence of a user 10 in the bathroom 12, using the sensor 40. Upon detection of the user 10, the analyzer may switch from a low power sleep mode into an active mode, so that the analyzer is prepared to receive and analyze the user’s exhaled breath. The analyzer 14 may use the sensor output to identify the user 10 as a specific individual stored in the memory of the control board 34, and optionally prompt the user 10 to confirm that identification. The user 10 may do so by voice, or via the finger pad 52 or the key pad 50. Absent confirmation, either by the analyzer alone or by the user 10, the analyzer 14 may set a prompt timer to activate a reminder to the user, so that the user exhale’s into the analyzer before leaving the bathroom. The reminder may be a visual or audible reminder. If the analyzer detects the user leaving the bathroom without exhaling into the analyzer, the analyzer may also activate a reminder.

[0020] Referring still to Fig. 3, as the user prepares to exhale into the analyzer 14, the user’s close presence may be detected by the proximity sensor, with the control board 34 then initiating certain operations, such as switching the fan 66 on. As the user exhales, the breath handling module 43 detects the user’s breath and control board may then operate to visibly or audibly indicate to the user that the analyzer 14 has successfully captured or received the user’s breath. The analyzer 14 then analyzes the breath particles, as described in U.S. Patent Application No. 17/571 ,363. The analyzer may then be saved in the memory, displayed, and/or communicated to other devices via the communication module 38. Where faster processing and greater memory are required to quickly perform analysis of the user’s breath, the analyzer 14 may transmit raw data via the communication module 38 to a remote computer. In a more basic form of the present methods, an analyzer 14 receives the user’s exhaled breath and performs the analysis, and one or all of the sensing, confirming, reminding steps etc. as described above may be omitted.

[0021] The user’s exhaled breath may include airborne metabolites which the analyzer 14 can detect and identify. Certain metabolites are associated with diseases such as influenza, depression, or diseases of the heart and lungs, and others. See the Human Metabolome Database at hmdb.ca/metabolites, incorporated herein by reference. The cells used in the cell assembly 64 may be adapted to respond to volatile and semi-volatile metabolites, the semi-volatile metabolites in one or more of the class of chemical compounds of saturated fatty acids (SFAs), hydrocarbons, alcohols, aldehydes, ketones, esters, phenols and alkaloids. [0022] As used here particle means a solid or a liquid droplet or aerosol particle in a user’s exhaled breath, sweat, urine, feces or saliva, including metabolites.

[0023] Figs. 7 and 8 show an alternative embodiment having a toilet water analyzer 84 and a breath analyzer 86 adjacent to a bathroom sink. The breath analyzer may always be on, continuously collecting air samples from the bathroom to provide a base line. In use the breath analyzer 86 collects breath samples via the user exhaling on or into it, or using a disposable straw or tube to deliver breath to the analyzer, depending on the sensitivity of the particle or metabolite to be measured.

[0024] In the embodiment of Fig. 7, a pipe 82 in the toilet delivers a small amount of water from the bowl to a liquid analyzer 84 for analyzing stool and/or urine deposited into the bowl. The toilet may include a sensor 86 for sensing deposition of, and/or the presence of, stool and/or urine in the toilet bowl. The sensor may be an optical, sound and/or a motion sensor. The sensor 86 is electrically linked to an electronic controller 88 in the liquid analyzer via a wire or wirelessly. When the sensor 86 is activated, the electronic controller may switch on a pump which pumps or aspirates a sample of water from the bowl into the liquid analyzer 84. In some designs the pump and the sensor may be omitted and the sample of water from the bowl is moved via capillary action or gravity into the liquid analyzer 84. Or the sensor 86 may be used to operate the system to prepare the biochip for receiving and analyzing the liquid sample. Alternatively, the sensor and the pump may both be omitted with a sample of water moved from the bowl to the liquid analyzer when the toilet is flushed. In this case the flushing force moves the sample of water into and through the analyzer, to an outlet of the analyzer, which returns the sample of water to a waste drain. A user sensor may optionally be used to detect a user sitting on the toilet seat or standing near the toilet.

[0025] Although the liquid analyzer 84 is shown in Fig. 7 as part of, or attached to, the toilet 80, the liquid analyzer 84 may optionally be provided as a separate unit or add on kit, supported e.g., on an adjacent wall, counter, etc. The liquid analyzer 84 may also optionally be attached externally onto, or placed in, the toilet tank. The description above applies as well to using the liquid analyzer 84 with a urinal instead of a toilet. [0026] The sample of water moves into a liquid flow path or channel in the liquid sample analyzer, Living cells in the liquid sample analyzer are separated from the liquid flow path via a membrane. The living cells may be attached to or supported on a first side of the membrane, which may be the bottom side of the membrane. The membrane may form a lower or bottom surface of the liquid flow path. As the sample of liquid moves through the liquid flow path, compounds or metabolites diffuse through the membrane and contact the living cells. The living cells selectively react to a compound or metabolite of interest by fluorescing. The fluorescing is detected by optical detectors, indicating the presence of a compound or metabolite of interest.

[0027] The liquid flow path has an inlet on a first side of the membrane and an outlet on a second side of the membrane. After flowing across the membrane, the sample of liquid moves to the outlet and then to a waste drain, which may be the waste drain of toilet or urinal that the sample of liquid was collected from. The biochip may operate with only a small volume of test sample liquid, for examplel 0 to 50 microliters.

[0028] The analyzers of Figs. 7 and 8 both locally analyze the collected samples and transmit resulting data to a remote server or computer. The computer compares the received data to a database and performs calculations to determine a health condition of the user. The computer transmits a result back to the user, optionally with a recommended course of action, suggested treatment. This may be displayed on the bathroom mirror, other display or in a message to smart phone or other appliance. It may also be sent to the user’s medical professionals. The analyzer 86 may optionally include a contact surface or port for receiving and analyzing saliva or perspiration, which may be applied with a swab.

[0029] The analyzer may include an infrared sensor for measuring the user’s temperature. In this embodiment, no visible light camera is used, and the infrared camera may be unfocused in view of bathroom privacy concerns. Optionally, both analyzers 84 and 86 may use the same underlying cell based operation. The cells may be contained in the biochip described in U.S. Patent Application No. 17/571 ,363, incorporated herein by reference, with the analyzers 84 and 86 adapted to operate with the bio chip receiving liquid and breath samples, respectively. Where a swab is used to apply a perspiration or saliva sample, the swab may be applied or rubbed directly on the membrane of the biochip. The optical sensors described in U.S. Patent Application No. 17/571,363 may be replaced by a large number of CMOS camera elements to provide a large number of channels. The biochip may be adapted to detect regulated and/or illegal drugs such as THC, ***e, amphetamines, narcotics, etc. The biochip may be adapted to detect a single substance, or multiple different substances.

[0030] Thus, novel systems and methods have been shown and described. Various changes and modifications may of course be made without departing from the spirit and scope of the invention. The invention, therefore, should not be limited, except by the following claims and their equivalents.

Claims

CLAIMS:

1. A method of detecting a health or medical condition of a patient, comprising: receiving the patient’s exhaled breath in an analyzer; exposing living cells in the analyzer to the breath; and identifying a compound in the breath based on a response from the living cells.

2. The method of claim 1 wherein the analyzer is in a bathroom.

3. The method of claim 1 wherein the response from the living cells is fluorescence.

4. The method of claim 1 wherein the compound is a metabolite indicative of a disease state.

5. The method of claim 1 further including displaying a message or analysis result on a display in the bathroom linked by wire or wirelessly to the analyzer.

6. The method of claim 5 wherein the displaying is on a mirror.

7. The method of claim 2 wherein the analyzer is mounted on a wall in the bathroom.

8. The method of claim 1 further including sensing the user exhaling towards, into or onto the analyzer and then initiating an analyzer operation.

9. A breath analyzer, comprising: a housing having an inlet and an outlet; a cell assembly in the housing, the cell assembly containing living cells; and an electronic controller in the housing for controlling operation of the cell assembly.

10. The breath analyzer of claim 9 wherein the housing is adapted for wall mounting.

11. A method of detecting a health or medical condition of a patient, comprising: receiving a water sample of the patient’s stool and/or urine from water in a bowl of a toilet, with the water sample provided from the bowl to an analyzer associated with the toilet; exposing living cells in the analyzer to the water; and identifying a compound in the breath based on a response from the living cells.

12. The method of claim 11 further including transmitting analyzed sample data from the analyzer to a computer, comparing the sample data to health state data stored in the computer, generating a recommendation for the user, and transmitting the recommendation to the user.

13. The method of claim 1 wherein the response from the living cells is fluorescence.

14. The method of claim 1 wherein the compound is a metabolite indicative of a disease state.

15. A method of detecting a health or medical condition of a patient, comprising: receiving a patient saliva or perspiration sample in an analyzer; exposing living cells in the analyzer to the sample; transmitting a result to a computer, the result based on a reaction of the living cells to the sample; the computer forming a recommendation for the user based on the result; and the computer transmitting the recommendation to the user.

16. The method of claim 15 wherein the computer compares the result to data stored in the computer to form the recommendation.

17. The method of claim 15 wherein the response from the living cells is fluorescence.

18. The method of claim 16 wherein the data stored in the computer includes metabolite profiles of patients having specific health or disease conditions.

19. The method of claim 15 wherein the exposing step is performed by pumping liquid containing the sample to a first side of a membrane with molecules of the sample moving through the membrane to the living cells on a second side of the membrane.

20. A liquid sample analyzer, comprising: a cell assembly in a housing, the cell assembly containing living cells; a liquid flow path in the housing; a membrane separating the living cells from the liquid flow path; a liquid inlet for providing a liquid sample from a liquid sample source into the liquid flow path; and an electronic controller in the housing for controlling operation of the cell assembly.

21 . The liquid sample analyzer of claim 20 wherein the liquid sample source is a toilet or a urinal.

22. The liquid sample analyzer of claim 20 further including a sensor for sensing a condition at the liquid sample source, the sensor electrically connected to the electronic controller.

23. The liquid sample analyzer of claim 20 wherein a liquid sample moves from the liquid sample source into the liquid flow path via capillary action.

24. The liquid sample analyzer of claim 20 wherein a liquid sample moves from the liquid sample source into the liquid flow path via gravity.

25. The liquid sample analyzer of claim 20 further including a tube extending from the liquid sample source to the liquid flow path for supplying a liquid sample to the liquid sample analyzer.

26. The liquid sample analyzer of claim 20 wherein the liquid flow path extends across the membrane to a liquid outlet.